徳島大学 / 教育研究者総覧 --- 玉置俊晃

個人のホームページ

https://researchmap.jp/read0019492 (researchmap)

専門分野

○	薬理学 (Pharmacology)

研究テーマ

○	腎臓薬理学, 循環薬理学 (腎循環 (renal circulation), 一酸化窒素 (nitric oxide), 酸化ストレス (oxidative stress), MAPキナーゼ (MAP kinase), 亜硝酸 (nitrous acid))

著書・論文

著書:

1.	玉置俊晃, 池田康将 : 疾病の成り立ちと回復の促進薬理学(第4版)(分担執筆各論4・5・6), 2023年10月.
2.	玉置俊晃 : 私と高血圧, 株式会社先端医学社, 2017年9月.
3.	池田康将, 玉置俊晃 : Annual Review2015腎臓---腎疾患と鉄代謝異常---, 株式会社中外医学社, 2015年1月.
4.	宮本理人, 山根萌, 冨田洋輔, 石澤啓介, 池田康将, 玉置俊晃, 土屋浩一郎 : ヒト腎糸球体内皮細胞における亜硝酸塩によるAMPK-eNOS活性化経路の検討, 株式会社東京医学社, 2014年10月.
5.	池田康将, 田島壮一郎, 木平孝高, 石澤有紀, 石澤啓介, 冨田修平, 土屋浩一郎, 玉置俊晃 : 腎とフリーラジカル第11集, --- 脂肪組織肥大進展における鉄キレート剤の効果 ---, 株式会社東京医学社, 東京, 2013年1月.
6.	櫻田巧, 石澤啓介, 今西正樹, 藤井聖子, 谷口順平, 石澤有紀, 宮本理人, 木平孝高, 池田康将, 冨田修平, 水口和生, 土屋浩一郎, 玉置俊晃 : 腎とフリーラジカル第11集, --- NitrosonifedipineはangiotensinⅡによるマウス血管リモデリングを抑制する ---, 株式会社東京医学社, 東京, 2013年1月.
7.	土屋浩一郎, 石澤啓介, 宮本理人, 堀ノ内裕也, 池田康将, 木平孝高, 冨田修平, 玉置俊晃 : 腎とフリーラジカル第11集, --- 亜硝酸塩による腎保護作用 ---, 株式会社東京医学社, 東京, 2013年1月.
8.	石澤啓介, 玉置俊晃, 他 : 疾患モデルの作製と利用-循環器疾患, LIFE-SCIENCE INFORMATION CENTER, 東京, 2010年8月.
9.	田島壮一郎, 土屋浩一郎, 濱本磨以, 久住祥子, 堀ノ内裕也, 八木祐子, 櫻田巧, 石澤啓介, 池田康将, 木平孝高, 冨田修平, 玉置俊晃 : 腎とフリーラジカル第10集, --- アンジオテンシンII刺激による細胞内遊離鉄を介した酸化ストレス増強機構 ---, 株式会社東京医学社, 東京, 2010年6月.
10.	大西秀樹, 土屋浩一郎, 田島壮一郎, 堀ノ内裕也, 福原弥生, 山口邦久, 石澤啓介, 冨田修平, 玉置俊晃 : 腎とフリーラジカル第9集, --- ハイドロエチジウム蛍光分析法による細胞内スーパーオキシド検出法の評価 ---, 株式会社東京医学社, 東京, 2008年9月.
11.	石澤啓介, 三木恵里加, 石澤有紀, 大西秀樹, Narantungalag Dorjsuren, 元林有紀, 山口邦久, 土屋浩一郎, 冨田修平, 玉置俊晃 : 腎とフリーラジカル第9集, --- オルメサルタンはPDGFによるメサンギウム細胞遊走を抑制する ---, 株式会社東京医学社, 東京, 2008年9月.

学術論文(審査論文):

1.	Toshiki Otoda, Akiko Sekine, Ryoko Uemoto, Seijiro Tsuji, Tomoyo Hara, Motoyuki Tamaki, Tomoyuki Yuasa, Toshiaki Tamaki, Munehide Matsuhisa and Ken-ichi Aihara : Albuminuria and Serum Tumor Necrosis Factor Receptor Levels in Patients with Type 2 Diabetes on SGLT2 Inhibitors: A Prospective Study., Diabetes Therapy, Vol.15, No.1, 127-143, 2023. (要約) (interquartile range (IQR) 23.1-28.9), and the median HbA1c level was 7.3% (IQR 6.9-8.3). After SGLT2i administration, the uACR declined from 19.2 mg/gCr (IQR 7.1-48.7) to 13.3 mg/gCr (IQR 7.5-31.6), whereas the uL-FABPCR was not influenced. In univariate analysis, the change in log-transformed uACR due to SGLT2i administration showed a positive correlation with the change in serum TNFR1 level (R = 0.244, p < 0.01). Multivariate regression analysis, including confounding factors, showed that the changes in serum TNFR1 level were independently associated with the changes in the log-transformed uACR (independent t = 2.102, p < 0.05). (徳島大学機関リポジトリ) ● Metadata: 119109 (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s13300-023-01488-0 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37883001 ● CiNii @ 国立情報学研究所 (CRID): 1050299749915184256 ● Summary page in Scopus @ Elsevier: 2-s2.0-85174952372 (徳島大学機関リポジトリ: 119109, DOI: 10.1007/s13300-023-01488-0, PubMed: 37883001, CiNii: 1050299749915184256, Elsevier: Scopus)
2.	Tomoyo Hara, Ryoko Uemoto, Akiko Sekine, Yukari Mitsui, Shiho Masuda, Hiroki Yamagami, Kiyoe Kurahashi, Sumiko Yoshida, Toshiki Otoda, Tomoyuki Yuasa, Akio Kuroda, Yasumasa Ikeda, Itsuro Endo, Soichi Honda, Katsuhiko Yoshimoto, Akira Kondo, Toshiaki Tamaki, Toshio Matsumoto, Munehide Matsuhisa, Masahiro Abe and Ken-ichi Aihara : Plasma Heparin Cofactor II Activity Is Inversely Associated with Hepatic Fibrosis of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus., Journal of Atherosclerosis and Thrombosis, 2022. (要約) Multiple regression analysis including confounding factors showed that plasma HCII activity independently contributed to decreases in FIB-4 index (p<0.001), NFS (p<0.001) and APRI (p=0.004). In addition, logistic regression analysis for the prevalence of advanced hepatic fibrosis defined by the cutoff points of the clinical scores showed that plasma HCII activity was the sole and common negative factor for prevalence of advanced hepatic fibrosis (FIB-4 index: p=0.002, NFS: p=0.026 and APRI: p=0.012). (徳島大学機関リポジトリ) ● Metadata: 118258 (出版サイトへのリンク) ● Publication site (DOI): 10.5551/jat.63752 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36244745 ● Search Scopus @ Elsevier (PMID): 36244745 ● Search Scopus @ Elsevier (DOI): 10.5551/jat.63752 (徳島大学機関リポジトリ: 118258, DOI: 10.5551/jat.63752, PubMed: 36244745)
3.	Yasumasa Ikeda, Hirofumi Hamano, Yuya Horinouchi, Licht Miyamoto, Hitayama Tasuku, Hideko Nagasawa, Toshiaki Tamaki and Koichiro Tsuchiya : Role of ferroptosis in cisplatin-induced acute nephrotoxicity in mice, Journal of Trace Elements in Medicine and Biology, Vol.67, 126798, 2021. (徳島大学機関リポジトリ) ● Metadata: 116131 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.jtemb.2021.126798 (文献検索サイトへのリンク) ● Search Scopus @ Elsevier (DOI): 10.1016/j.jtemb.2021.126798 (徳島大学機関リポジトリ: 116131, DOI: 10.1016/j.jtemb.2021.126798)
4.	Tomoyo Hara, Ryoko Uemoto, Akiko Sekine, Yukari Mitsui, Shiho Masuda, Kiyoe Kurahashi, Sumiko Yoshida, Toshiki Otoda, Tomoyuki Yuasa, Akio Kuroda, Yasumasa Ikeda, Itsuro Endo, Soichi Honda, Katsuhiko Yoshimoto, Akira Kondo, Toshiaki Tamaki, Toshio Matsumoto, Munehide Matsuhisa, Masahiro Abe and Ken-ichi Aihara : Plasma Heparin Cofactor II Activity Is Inversely Associated with Albuminuria and Its Annual Deterioration in Patients with Diabetes., Journal of Diabetes Investigation, 2021. (要約) The plasma HCII activity was inversely and specifically associated with glomerular injury in patients with diabetes. The results suggest that HCII can serve as a novel predictive factor for early-stage DKD development, as represented by albuminuria. (徳島大学機関リポジトリ) ● Metadata: 116545 (出版サイトへのリンク) ● Publication site (DOI): 10.1111/jdi.13602 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34043882 ● Search Scopus @ Elsevier (PMID): 34043882 ● Search Scopus @ Elsevier (DOI): 10.1111/jdi.13602 (徳島大学機関リポジトリ: 116545, DOI: 10.1111/jdi.13602, PubMed: 34043882)
5.	石澤有紀, 合田光寛, 相澤風花, 座間味義人, 濱野裕章, 八木健太, 池田康将, 石澤啓介, 玉置俊晃 : 薬剤誘発性大動脈解離易発症モデルマウスを用いた薬効評価, 四国医学雑誌, Vol.77, No.1,2, 57-62, 2021年. (要約) Aortic dissection (or dissecting aortic aneurysm) is a condition in which the aortic wall is separated into two layers at the medial level to form a pseudocavity. The intima crack, called the ``entry'', allows blood to tear through the medial layer and flow in. The location of the ``entry'' and the extent of the dissection can cause a variety of serious complications, including rupture, cardiac tamponade, and obstruction of branched vessels. According to the Guideline on Diagnosis and Treatment of Aortic Aneurysm and Aortic Dissection 2020, it is estimated that 61.4% of the onset of dissection die before arrival at the hospital, and 93% will die within 24 hours after the onset. It has been suggested that the morbidity rate has been increasing in recent years. Since many of them have a fatal prognosis, it is an important issue to prevent the onset itself. However, no effective therapeutic agent or preventive strategy has been established so far. The first reason is that it is extremely difficult to design clinical studies because aortic dissection traced the rapid onset and progression. The second is that the pathophysiology and preventive drug search are not sufficiently conducted even at the basic research level. Epidemiologically, the results of the International Registry of Aortic Dissection (IRAD) revealed that aging, hypertension, atherosclerosis, and hereditary connective tissue diseases are risk factors. The aortic aneurysm also shows similar pathological conditions caused by these risk factors. However, one of the major differences between aneurysm and dissection is the presence of aortic intima rupture. Therefore, we attempted to establish a mouse model developing dissection at a high rate by adding the endothelial dysfunction to a pharmacologically induced aortic aneurysm model mouse. Furthermore, we evaluated the efficacy of pitavastatin and several nutrients using our novel model mice and verified its usefulness as a model animal. (キーワード) aortic dissection / endothelial dysfunction / statin / polyphenol / large medical databases (徳島大学機関リポジトリ) ● Metadata: 116038 (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1050851320431028352 (徳島大学機関リポジトリ: 116038, CiNii: 1050851320431028352)
6.	Hirofumi Hamano, Yasumasa Ikeda, Mitsuhiro Goda, Keijo Fukushima, Seiji Kishi, Masayuki Chuma, Michiko Yamashita, Takahiro Niimura, Kenshi Takechi, Masaki Imanishi, Yoshito Zamami, Yuya Horinouchi, Izawa-Ishizawa Yuki, Licht Miyamoto, Ishizawa Keisuke, Hiromichi Fujino, Toshiaki Tamaki, Ken-ichi Aihara and Koichiro Tsuchiya : Diphenhydramine may be a preventive medicine against cisplatin-induced kidney toxicity, Kidney International, Vol.99, No.4, 885-889, 2021. (要約) Cisplatin is widely used as an anti-tumor drug for the treatment of solid tumors. Unfortunately, it causes kidney toxicity as a critical side effect, limiting its use, given that no preventive drug against cisplatin-induced kidney toxicity is currently available. Here, based on a repositioning analysis of the Food and Drug Administration Adverse Events Reporting System, we found that a previously developed drug, diphenhydramine, may provide a novel treatment for cisplatin-induced kidney toxicity. To confirm this, the actual efficacy of diphenhydramine was evaluated in in vitro and in vivo experiments. Diphenhydramine inhibited cisplatin-induced cell death in kidney proximal tubular cells. Mice administered cisplatin developed kidney injury with significant dysfunction (mean plasma creatinine: 0.43 vs 0.15 mg/dl) and showed augmented oxidative stress, increased apoptosis, elevated inflammatory cytokines, and MAPKs activation. However, most of these symptoms were suppressed by treatment with diphenhydramine. Furthermore, the concentration of cisplatin in the kidney was significantly attenuated in diphenhydramine-treated mice (mean platinum content: 70.0 vs 53.4 μg/g dry kidney weight). Importantly, diphenhydramine did not influence or interfere with the anti-tumor effect of cisplatin in any of the in vitro or in vivo experiments. In a selected cohort of 98 1:1 matched patients from a retrospective database of 1467 patients showed that patients with malignant cancer who had used diphenhydramine before cisplatin treatment exhibited significantly less acute kidney injury compared to ones who did not (6.1 % vs 22.4 %, respectively). Thus, diphenhydramine demonstrated efficacy as a novel preventive medicine against cisplatin-induced kidney toxicity. (徳島大学機関リポジトリ) ● Metadata: 115399 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.kint.2020.10.041 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33307103 ● Search Scopus @ Elsevier (PMID): 33307103 ● Search Scopus @ Elsevier (DOI): 10.1016/j.kint.2020.10.041 (徳島大学機関リポジトリ: 115399, DOI: 10.1016/j.kint.2020.10.041, PubMed: 33307103)
7.	Yasumasa Ikeda, Hiroaki Watanabe, Tetsuya Shiuchi, Hirofumi Hamano, Yuya Horinouchi, Masaki Imanishi, Mitsuhiro Goda, Yoshito Zamami, Kenshi Takechi, Yuki Izawa-Ishizawa, Licht Miyamoto, Keisuke Ishizawa, Ken-ichi Aihara, Koichiro Tsuchiya and Toshiaki Tamaki : Deletion of H-ferritin in macrophages alleviates obesity and diabetes induced by high-fat diet in mice, Diabetologia, Vol.63, No.8, 1588-1602, 2020. (要約) Iron accumulation affects obesity and diabetes, both of which are ameliorated by iron reduction. Ferritin, an iron-storage protein, plays a crucial role in iron metabolism. H-ferritin exerts its cytoprotective action by reducing toxicity via its ferroxidase activity. We investigated the role of macrophage H-ferritin in obesity and diabetes. Conditional macrophage-specific H-ferritin (Fth, also known as Fth1) knockout (LysM-Cre Fth KO) mice were used and divided into four groups: wild-type (WT) and LysM-Cre Fth KO mice with normal diet (ND), and WT and LysM-Cre Fth KO mice with high-fat diet (HFD). These mice were analysed for characteristics of obesity and diabetes, tissue iron content, inflammation, oxidative stress, insulin sensitivity and metabolic measurements. RAW264.7 macrophage cells were used for in vitro experiments. Iron concentration reduced, and mRNA expression of ferroportin increased, in macrophages from LysM-Cre Fth KO mice. HFD-induced obesity was lower in LysM-Cre Fth KO mice than in WT mice at 12 weeks (body weight: KO 34.6 ± 5.6 g vs WT 40.1 ± 5.2 g). mRNA expression of inflammatory cytokines and infiltrated macrophages and oxidative stress increased in the adipose tissue of HFD-fed WT mice, but was not elevated in HFD-fed LysM-Cre Fth KO mice. However, WT mice fed an HFD had elevated iron concentration in adipose tissue and spleen, which was not observed in LysM-Cre Fth KO mice fed an HFD (adipose tissue [μmol Fe/g protein]: KO 1496 ± 479 vs WT 2316 ± 866; spleen [μmol Fe/g protein]: KO 218 ± 54 vs WT 334 ± 83). Moreover, HFD administration impaired both glucose tolerance and insulin sensitivity in WT mice, which was ameliorated in LysM-Cre Fth KO mice. In addition, energy expenditure, mRNA expression of thermogenic genes, and body temperature were higher in KO mice with HFD than WT mice with HFD. In vitro experiments showed that iron content was reduced, and lipopolysaccharide-induced Tnf-α (also known as Tnf) mRNA upregulation was inhibited in a macrophage cell line transfected with Fth siRNA. Deletion of macrophage H-ferritin suppresses the inflammatory response by reducing intracellular iron levels, resulting in the prevention of HFD-induced obesity and diabetes. The findings from this study highlight macrophage iron levels as a potential therapeutic target for obesity and diabetes. (徳島大学機関リポジトリ) ● Metadata: 114409 (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s00125-020-05153-0 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32430665 ● Summary page in Scopus @ Elsevier: 2-s2.0-85085484596 (徳島大学機関リポジトリ: 114409, DOI: 10.1007/s00125-020-05153-0, PubMed: 32430665, Elsevier: Scopus)
8.	Tatsuya Tsuda, Masaki Imanishi, Mizuho Oogoshi, Mitsuhiro Goda, Yoshitaka Kihira, Yuya Horinouchi, Yoshito Zamami, Keisuke Ishizawa, Yasumasa Ikeda, Ichiro Hashimoto, Toshiaki Tamaki and Yuki Izawa-Ishizawa : Rho-associated protein kinase and cyclophilin a are involved in inorganic phosphate-induced calcification signaling in vascular smooth muscle cells., Journal of Pharmacological Sciences, Vol.142, No.3, 109-115, 2020. (要約) Arterial calcification, a risk factor of cardiovascular events, develops with differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Cyclophilin A (CypA) is a peptidyl-prolyl isomerase involved in cardiovascular diseases such as atherosclerosis and aortic aneurysms, and rho-associated protein kinase (ROCK) is involved in the pathogenesis of vascular calcification. CypA is secreted in a ROCK activity-dependent manner and works as a mitogen via autocrine or paracrine mechanisms in VSMCs. We examined the involvement of the ROCK-CypA axis in VSMC calcification induced by inorganic phosphate (Pi), a potent cell mineralization initiator. We found that Pi stimulated ROCK activity, CypA secretion, extracellular signal-regulated protein kinase (ERK) 1/2 phosphorylation, and runt-related transcription factor 2 expression, resulting in calcium accumulation in rat aortic smooth muscle cells (RASMCs). The ROCK inhibitor Y-27632 significantly suppressed Pi-induced CypA secretion, ERK1/2 phosphorylation, and calcium accumulation. Recombinant CypA was found to be associated with increased calcium accumulation in RASMCs. Based on these results, we suggest that autocrine CypA is mediated by ROCK activity and is involved in Pi-induced ERK1/2 phosphorylation following calcification signaling in RASMCs. (徳島大学機関リポジトリ) ● Metadata: 115530 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.jphs.2019.12.005 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31882204 ● Search Scopus @ Elsevier (PMID): 31882204 ● Search Scopus @ Elsevier (DOI): 10.1016/j.jphs.2019.12.005 (徳島大学機関リポジトリ: 115530, DOI: 10.1016/j.jphs.2019.12.005, PubMed: 31882204)
9.	Hirofumi Hamano, Takahiro Niimura, Yuya Horinouchi, Yoshito Zamami, Kenshi Takechi, Mitsuhiro Goda, Masaki Imanishi, Masayuki Chuma, Yuki Izawa-Ishizawa, Licht Miyamoto, Keijo Fukushima, Hiromichi Fujino, Koichiro Tsuchiya, Keisuke Ishizawa, Toshiaki Tamaki and Yasumasa Ikeda : Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway, Toxicology Letters, Vol.318, 86-91, 2020. (要約) Proton pump inhibitors (PPIs) have been used worldwide to treat gastrointestinal disorders. A recent study showed that long-term use of PPIs caused iron deficiency; however, it is unclear whether PPIs affect iron metabolism directly. We investigated the effect of PPIs on the peptide hepcidin, an important iron regulatory hormone. First, we used the FDA Adverse Event Reporting System database and analyzed the influence of PPIs. We found that PPIs, as well as H2 blockers, increased the odds ratio of iron-deficient anemia. Next, HepG2 cells were used to examine the action of PPIs and H2 blockers on hepcidin. PPIs augmented hepcidin expression, while H2 blockers did not. In fact, the PPI omeprazole increased hepcidin secretion, and omeprazole-induced hepcidin upregulation was inhibited by gene silencing or the pharmacological inhibition of the aryl hydrocarbon receptor. In mouse experiments, omeprazole also increased hepatic hepcidin mRNA expression and blood hepcidin levels. In mice treated with omeprazole, protein levels of duodenal and splenic ferroportin decreased. Taken together, PPIs directly affect iron metabolism by suppressing iron absorption through the inhibition of duodenal ferroportin via hepcidin upregulation. These findings provide a new insight into the molecular mechanism of PPI-induced iron deficiency. (徳島大学機関リポジトリ) ● Metadata: 113812 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.toxlet.2019.10.016 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31669099 ● Search Scopus @ Elsevier (PMID): 31669099 ● Search Scopus @ Elsevier (DOI): 10.1016/j.toxlet.2019.10.016 (徳島大学機関リポジトリ: 113812, DOI: 10.1016/j.toxlet.2019.10.016, PubMed: 31669099)
10.	Yasumasa Ikeda, Akiho Satoh, Yuya Horinouchi, Hirofumi Hamano, Hiroaki Watanabe, Mizuki Imao, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Yuki Izawa-Ishizawa, Licht Miyamoto, Hirayama Tasuku, Hideko Nagasawa, Keisuke Ishizawa, Ken-ichi Aihara, Koichiro Tsuchiya and Toshiaki Tamaki : Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress, The FASEB journal, Vol.33, No.8, 9551-9564, 2019. (要約) Skeletal muscle atrophy is caused by disruption in the homeostatic balance of muscle degeneration and regeneration under various pathophysiological conditions. We have previously reported that iron accumulation induces skeletal muscle atrophy a ubiquitin ligase-dependent pathway. However, the potential effect of iron accumulation on muscle regeneration remains unclear. To examine the effect of iron accumulation on myogenesis, we used a mouse model with cardiotoxin (CTX)-induced muscle regeneration and C2C12 mouse myoblast cells . In mice with iron overload, the skeletal muscles exhibited increased oxidative stress and decreased expression of satellite cell markers. Following CTX-induced muscle injury, these mice also displayed delayed muscle regeneration with a decrease in the size of regenerating myofibers, reduced expression of myoblast differentiation markers, and decreased phosphorylation of MAPK signaling pathways. , iron overload also suppressed the differentiation of C2C12 myoblast cells but the suppression could be reversed by superoxide scavenging using tempol. Excess iron inhibits myogenesis oxidative stress, leading to an imbalance in skeletal muscle homeostasis.-Ikeda, Y., Satoh, A., Horinouchi, Y., Hamano, H., Watanabe, H., Imao, M., Imanishi, M., Zamami, Y., Takechi, K., Izawa-Ishizawa, Y., Miyamoto, L., Hirayama, T., Nagasawa, H., Ishizawa, K., Aihara, K.-I., Tsuchiya, K., Tamaki, T. Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress. (徳島大学機関リポジトリ) ● Metadata: 113746 (出版サイトへのリンク) ● Publication site (DOI): 10.1096/fj.201802724RR (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31145863 ● Search Scopus @ Elsevier (PMID): 31145863 ● Search Scopus @ Elsevier (DOI): 10.1096/fj.201802724RR (徳島大学機関リポジトリ: 113746, DOI: 10.1096/fj.201802724RR, PubMed: 31145863)
11.	Hirofumi Hamano, Marin Mitsui, Yoshito Zamami, Kenshi Takechi, Takahiro Nimura, Naoto Okada, Keijo Fukushima, Masaki Imanishi, Masayuki Chuma, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yasushi Kirino, Toshimi Nakamura, Kazuhiko Teraoka, Yasumasa Ikeda, Hiromichi Fujino, Hiroaki Yanagawa, Toshiaki Tamaki and Keisuke Ishizawa : Irinotecan-induced neutropenia is reduced by oral alkalization drugs: analysis using retrospective chart reviews and the spontaneous reporting database., Supportive Care in Cancer, Vol.27, No.3, 849-856, 2019. (要約) These data indicate that oral alkalization drugs may reduce the frequency of neutropenia caused by irinotecan administration, making it possible to increase the dose safely. (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s00520-018-4367-y (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30062585 ● Search Scopus @ Elsevier (PMID): 30062585 ● Search Scopus @ Elsevier (DOI): 10.1007/s00520-018-4367-y (DOI: 10.1007/s00520-018-4367-y, PubMed: 30062585)
12.	Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Toya Hiroki, Nagao Tomoko, Marin Morishita, Koichi Tsuneyama, Yuya Horinouchi, Yoshitaka Kihira, Kenshi Takechi, Yasumasa Ikeda, Koichiro Tsuchiya, Masanori Yoshizumi, Toshiaki Tamaki and Keisuke Ishizawa : Development of a novel aortic dissection mouse model and evaluation of drug efficacy using in-vivo assays and database analyses., Journal of Hypertension, Vol.37, No.1, 73-83, 2019. (要約) Aortic dissection is a life-threatening disease. At present, the only therapeutic strategies available are surgery and antihypertensive drugs. Moreover, the molecular mechanisms underlying the onset of aortic dissection are still unclear. We established a novel aortic dissection model in mice using pharmacologically induced endothelial dysfunction. We then used the Japanese Adverse Drug Event Report database to investigate the role of pitavastatin in preventing the onset of aortic dissection. To induce endothelial dysfunction, Nω-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, was administered to C57BL/6 mice. Three weeks later, angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, were administered with osmotic mini-pumps. False lumen formation was used as the pathological determinant of aortic dissection. The incidences of aortic dissection and death from aneurysmal rupture were significantly higher in the Nω-nitro-L-arginine methyl ester, Ang II, and BAPN (LAB) group than they were in the Ang II and BAPN (AB) group.Pitavastatin was administered orally to LAB mice. It significantly lowered the incidences of dissection and rupture. It also decreased inflammation and medial degradation, both of which were exacerbated in the LAB group. The Japanese Adverse Drug Event Report database analysis indicated that there were 113 cases of aortic dissection out of 95 090 patients (0.12%) not receiving statins but only six cases out of 16 668 patients receiving statins (0.04%) (odds ratio: 0.30; P = 0.0043). Our results suggest that endothelial dysfunction is associated with the onset of aortic dissection and pitavastatin can help prevent this condition. (徳島大学機関リポジトリ) ● Metadata: 113264 (出版サイトへのリンク) ● Publication site (DOI): 10.1097/HJH.0000000000001898 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30303488 ● Search Scopus @ Elsevier (PMID): 30303488 ● Search Scopus @ Elsevier (DOI): 10.1097/HJH.0000000000001898 (徳島大学機関リポジトリ: 113264, DOI: 10.1097/HJH.0000000000001898, PubMed: 30303488)
13.	Masaki Imanishi, Yuki Izawa-Ishizawa, T Sakurada, Y Kohara, Yuya Horinouchi, E Sairyo, Yoshito Zamami, Kenshi Takechi, Masayuki Chuma, Keijo Fukushima, Yasumasa Ikeda, Hiromichi Fujino, M Yoshizumi, Koichiro Tsuchiya, Toshiaki Tamaki and Keisuke Ishizawa : Nitrosonifedipine, a Photodegradation Product of Nifedipine, Suppresses Pharmacologically Induced Aortic Aneurysm Formation., Pharmacology, Vol.102, No.5-6, 281-286, 2018. (要約) We have reported that nitrosonifedipine (NO-NIF), a photodegradation product of nifedipine, has strong antioxidant and endothelial protective effects, and can suppress several cardiovascular diseases in animal models. The objective of the present study was to investigate the effects of NO-NIF on aortic aneurysm formation. The mice were infused with β-aminopropionitrile for 2 weeks and angiotensin II for 6 weeks to induce aortic aneurysm formation. The oxidative stress was measured by dihydroethidium staining and nitrotyrosine staining. The expressions of inflammation-related genes were assessed by quantitative real-time PCR and immunohistochemical staining. To clarify the mechanisms of how NO-NIF suppresses vascular cell adhesion molecule (VCAM)-1, endothelial cells were used in in vitro system. NO-NIF suppressed pharmacologically induced the aortic aneurysm formation and aortic expansion without blood pressure changes. NO-NIF suppressed elastin degradation and matrix metalloproteinase-2 mRNA expression. NO-NIF suppressed the reactive oxygen species-cyclophilin A positive feedback loop. Upregulated mRNA expressions of inflammation-related genes and endothelial VCAM-1 were suppressed by NO-NIF co-treatment in aortae. NO-NIF has the potential to be a new, nifedipine-derived therapeutic drug for suppressing aortic aneurysm formation by directly improving aortic structure with its strong ability to reduce oxidative stress and inflammation. (キーワード) Aminopropionitrile / Angiotensin II / Animals / Antigens, Differentiation / Antioxidants / Aortic Aneurysm / Chemokine CCL2 / Cyclophilins / Disease Models, Animal / Elastin / Endothelial Cells / Human Umbilical Vein Endothelial Cells / Humans / Male / Matrix Metalloproteinase 2 / Mice / Nifedipine / Nitroso Compounds / Oxidative Stress / Photolysis / Reactive Oxygen Species / Vascular Cell Adhesion Molecule-1 (出版サイトへのリンク) ● Publication site (DOI): 10.1159/000492577 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30253416 ● Summary page in Scopus @ Elsevier: 2-s2.0-85054191604 (DOI: 10.1159/000492577, PubMed: 30253416, Elsevier: Scopus)
14.	Yuya Horinouchi, Yasumasa Ikeda, Keijo Fukushima, Masaki Imanishi, Hirofumi Hamano, Yuki Izawa-Ishizawa, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Hiromichi Fujino, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis., Scientific Reports, Vol.8, No.1, 2018. (要約) Renal tubulointerstitial injury, an inflammation-associated condition, is a major cause of chronic kidney disease (CKD). Levels of activated factor X (FXa), a blood coagulation factor, are increased in various inflammatory diseases. Therefore, we investigated the protective effects of an FXa inhibitor against renal tubulointerstitial injury using unilateral ureteral obstruction (UUO) mice (a renal tubulointerstitial fibrosis model) and the Food and Drug Administration Adverse Events Reporting System (FAERS) database. The renal expression levels of FX and the FXa receptors protease-activated receptor (PAR)-1 and PAR-2 were significantly higher in UUO mice than in sham-operated mice. UUO-induced tubulointerstitial fibrosis and extracellular matrix expression were suppressed in UUO mice treated with the FXa inhibitor edoxaban. Additionally, edoxaban attenuated UUO-induced macrophage infiltration and inflammatory molecule upregulation. In an analysis of the FAERS database, there were significantly fewer reports of tubulointerstitial nephritis for patients treated with FXa inhibitors than for patients not treated with inhibitors. These results suggest that FXa inhibitors exert protective effects against CKD by inhibiting tubulointerstitial fibrosis. (徳島大学機関リポジトリ) ● Metadata: 112445 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/s41598-018-29008-2 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30022146 ● Search Scopus @ Elsevier (PMID): 30022146 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-018-29008-2 (徳島大学機関リポジトリ: 112445, DOI: 10.1038/s41598-018-29008-2, PubMed: 30022146)
15.	Hirofumi Hamano, Yasumasa Ikeda, Hiroaki Watanabe, Yuya Horinouchi, Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : The uremic toxin indoxyl sulfate interferes with iron metabolism by regulating hepcidin in chronic kidney disease, Nephrology, Dialysis, Transplantation, Vol.33, No.4, 586-597, 2018. (徳島大学機関リポジトリ) ● Metadata: 110922 (出版サイトへのリンク) ● Publication site (DOI): 10.1093/ndt/gfx252 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28992067 ● Search Scopus @ Elsevier (PMID): 28992067 ● Search Scopus @ Elsevier (DOI): 10.1093/ndt/gfx252 (徳島大学機関リポジトリ: 110922, DOI: 10.1093/ndt/gfx252, PubMed: 28992067)
16.	Wenting Xu, Licht Miyamoto, Haruna Aihara, Tomomi Yamaoka, Naonobu Tanaka, Yuki Tsuchihashi, Yasumasa Ikeda, Toshiaki Tamaki, Yoshiki Kashiwada and Koichiro Tsuchiya : Methanol extraction fraction from Citrus Sudachi peel exerts lipid reducing effects in cultured cells., The Journal of Medical Investigation : JMI, Vol.65, No.3.4, 225-230, 2018. (要約) Ectopic fat accumulation is associated with insulin resistance and type 2 diabetes mellitus. Citrus sudachi is an evergreen tree that is found mainly in Tokushima Prefecture in Japan. Previously, it was demonstrated that Citrus sudachi could inhibit the rising trend of blood glucose and fatty acid in human subjects. In the current study, we illustrated the function of methanol extracts from sudachi peel and investigated the mechanism of this effect. We got the five kinds of methanol extracts by using diaion HP-20, and those were named by hydrophobicity from M-F1 to M-F5. Among the 5 kinds of sudachi methanol extracts, only M-F4 significantly decreased the intracellular triglyceride of C2C12 cells. It augmented the AMPK activity and increased the transcription of PPARα and its downstream targets CPT-1b and UCP2. In conclusion, M-F4 improved the lipid metabolism possibly through AMPK, PPARα and their downstream targets like CPT-1b and UCP2. Furthermore, this extract may be useful for preventing obesity and diabetes related diseases. J. Med. Invest. 65:225-230, August, 2018. (キーワード) AMP-Activated Protein Kinases / Animals / Cell Line / Citrus / Humans / Hypolipidemic Agents / Lipid Metabolism / メタノール (methanol) / ノックアウトマウス (knockout mice) / Models, Biological / PPAR alpha / Phytotherapy / Plant Extracts / シグナル伝達 (signal transduction) / Sirtuin 1 / Triglycerides (徳島大学機関リポジトリ) ● Metadata: 112243 (出版サイトへのリンク) ● Publication site (DOI): 10.2152/jmi.65.225 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30282865 ● Search Scopus @ Elsevier (PMID): 30282865 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.65.225 (徳島大学機関リポジトリ: 112243, DOI: 10.2152/jmi.65.225, PubMed: 30282865)
17.	Katsunori Tsuda, Licht Miyamoto, Shuichi Hamano, Yuri Morimoto, Yumi Kangawa, Chika Fukue, Yoko Kagawa, Yuya Horinouchi, Wenting Xu, Yasumasa Ikeda, Toshiaki Tamaki and Koichiro Tsuchiya : Mechanisms of the pH- and Oxygen-Dependent Oxidation Activities of Artesunate., Biological & Pharmaceutical Bulletin, Vol.41, No.4, 555-563, 2018. (要約) Artemisinin was discovered in 1971 as a constituent of the wormwood genus plant (Artemisia annua). This plant has been used as an herbal medicine to treat malaria since ancient times. The compound artemisinin has a sesquiterpene lactone bearing a peroxide group that offers its biological activity. In addition to anti-malarial activity, artemisinin derivatives have been reported to exert antitumor activity in cancer cells, and have attracted attention as potential anti-cancer drugs. Mechanisms that might explain the antitumor activities of artemisinin derivatives reportedly induction of apoptosis, angiogenesis inhibitory effects, inhibition of hypoxia-inducible factor-1 (HIF-1) activation, and direct DNA injury. Reactive oxygen species (ROS) generation is involved in many cases. However, little is known about the mechanism of ROS formation from artemisinin derivatives and what types of ROS are produced. Therefore, we investigated the iron-induced ROS formation mechanism by using artesunate, a water-soluble artemisinin derivative, which is thought to be the underlying mechanism involved in artesunate-mediated cell death. The ROS generated by the coexistence of iron(II), artesunate, and molecular oxygen was a hydroxyl radical or hydroxyl radical-like ROS. Artesunate can reduce iron(III) to iron(II), which enables generation of ROS irrespective of the iron valence. We found that reduction from iron(III) to iron(II) was activated in the acidic rather than the neutral region and was proportional to the hydrogen ion concentration. (出版サイトへのリンク) ● Publication site (DOI): 10.1248/bpb.b17-00855 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29607928 ● Search Scopus @ Elsevier (PMID): 29607928 ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b17-00855 (DOI: 10.1248/bpb.b17-00855, PubMed: 29607928)
18.	Takahiro Niimura, Yoshito Zamami, Toshihiro Koyama, Yuki Izawa-Ishizawa, Masashi Miyake, Tadashi Koga, Keisaku Harada, Ayako Ohshima, Toru Imai, Yutaka Kondo, Masaki Imanishi, Kenshi Takechi, Keijo Fukushima, Yuya Horinouchi, Yasumasa Ikeda, Hiromichi Fujino, Koichiro Tsuchiya, Toshiaki Tamaki, Shiro Hinotsu, R Mitsunobu Kano and Keisuke Ishizawa : Hydrocortisone administration was associated with improved survival in Japanese patients with cardiac arrest., Scientific Reports, Vol.7, No.1, 2017. (要約) There are few reports on hydrocortisone administration after cardiac arrest, and those that have been published included few subjects. This study aimed to evaluate the effect of hydrocortisone administration on the outcomes of patients who experienced cardiac arrest. We investigated the survival discharge rates and the length of hospital stay from cardiac arrest to discharge, stratified by use of hydrocortisone, using a Japanese health-insurance claims dataset that covers approximately 2% of the Japanese population. The study included the data of 2233 subjects who experienced either in-hospital or out-of-hospital cardiac arrest between January 2005 and May 2014. These patients were divided into two groups, based on the administration of hydrocortisone. We adjusted the baseline characteristics, medical treatment, and drug administration data of the two groups using propensity scores obtained via the inverse probability of treatment weighted method. The hydrocortisone group had a significantly higher survival discharge rate (13/61 [21.1%] vs. 240/2172 [11.0%], adjusted odds ratio: 4.2, 95% CI: 1.60-10.98, p = 0.004). In addition, the administration of hydrocortisone was independent predictor of survival to discharge (hazard ratio: 4.6, p < 0.001). The results demonstrate a correlation between hydrocortisone administration and the high rates of survival to discharge. (徳島大学機関リポジトリ) ● Metadata: 112397 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/s41598-017-17686-3 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29263333 ● Search Scopus @ Elsevier (PMID): 29263333 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-017-17686-3 (徳島大学機関リポジトリ: 112397, DOI: 10.1038/s41598-017-17686-3, PubMed: 29263333)
19.	Yasumasa Ikeda, Yuya Horinouchi, Hamano Hirofumi, Hirayama Tasuku, Seiji Kishi, Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Keisuke Ishizawa, Ken-ichi Aihara, Hideko Nagasawa, Koichiro Tsuchiya and Toshiaki Tamaki : Dietary iron restriction alleviates renal tubulointerstitial injury induced by protein overload in mice, Scientific Reports, Vol.7, No.1, 10621, 2017. (要約) Increased proteinuria causes tubulointerstitial injury due to inflammation in chronic kidney disease (CKD). Iron restriction exhibits protective effects against renal dysfunction; however, its effects against protein overload-induced tubulointerstitial damage remain unclear. Here, we investigated dietary iron restriction effect on tubulointerstitial damage in mice with protein-overload tubulointerstitial injury. Renal tubulointerstitial injury in animal model was induced by intraperitoneal injection of an overdose of bovine serum albumin (BSA). We divided mice into three groups: normal saline + normal diet (ND), BSA + ND, and BSA + iron-restricted diet (IRD). BSA overload induced renal tubulointerstitial injury in the ND mice, which was ameliorated in the IRD mice. Inflammatory cytokines and extracellular matrix mRNA expression was upregulated in BSA + ND mice kidneys and was inhibited by IRD. BSA-induced increase in renal superoxide production, NADPH oxidase activity, and p22(phox) expression was diminished in the IRD mice. IRD suppression increased BSA-induced renal macrophage infiltration. Moreover, BSA mice exhibited nucleotide-binding oligomerisation domain-like receptor pyrin domain-containing protein (NLRP) inflammasome activation, which was inhibited by IRD. Ferrous iron increased in kidneys with BSA overload and was inhibited by IRD. Thus, iron restriction inhibited oxidative stress and inflammatory changes, contributing to the protective effect against BSA overload-induced tubulointerstitial injury. (徳島大学機関リポジトリ) ● Metadata: 112368 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/s41598-017-11089-0 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28878231 ● Search Scopus @ Elsevier (PMID): 28878231 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-017-11089-0 (徳島大学機関リポジトリ: 112368, DOI: 10.1038/s41598-017-11089-0, PubMed: 28878231)
20.	Keisuke Oshima, Yasumasa Ikeda, Yuya Horinouchi, Hiroaki Watanabe, Hirofumi Hamano, Yoshitaka Kihira, Seiji Kishi, Yuki Izawa-Ishizawa, Licht Miyamoto, Tasuku Hirayama, Hideko Nagasawa, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Iron suppresses erythropoietin expression via oxidative stress-dependent hypoxia-inducible factor-2 alpha inactivation, Laboratory Investigation; a Journal of Technical Methods and Pathology, Vol.97, No.5, 555-566, 2017. (要約) Renal anemia is a major complication in chronic kidney disease (CKD). Iron supplementation, as well as erythropoiesis-stimulating agents, are widely used for treatment of renal anemia. However, excess iron causes oxidative stress via the Fenton reaction, and iron supplementation might damage remnant renal function including erythropoietin (EPO) production in CKD. EPO gene expression was suppressed in mice following direct iron treatment. Hypoxia-inducible factor-2 alpha (HIF-2α), a positive regulator of the EPO gene, was also diminished in the kidney of mice following iron treatment. Anemia-induced increase in renal EPO and HIF-2α expression was inhibited by iron treatment. In in vitro experiments using EPO-producing HepG2 cells, iron stimulation reduced the expression of the EPO gene, as well as HIF-2α. Moreover, iron treatment augmented oxidative stress, and iron-induced reduction of EPO and HIF-2α expression was restored by tempol, an antioxidant compound. HIF-2α interaction with the Epo promoter was inhibited by iron treatment, and was restored by tempol. These findings suggested that iron supplementation reduced EPO gene expression via an oxidative stress-HIF-2α-dependent signaling pathway. (徳島大学機関リポジトリ) ● Metadata: 113749 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/labinvest.2017.11 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28263291 ● Search Scopus @ Elsevier (PMID): 28263291 ● Search Scopus @ Elsevier (DOI): 10.1038/labinvest.2017.11 (徳島大学機関リポジトリ: 113749, DOI: 10.1038/labinvest.2017.11, PubMed: 28263291)
21.	Yutaka Fukunaga, Yuki Izawa-Ishizawa, Yuya Horinouchi, Eriko Sairyo, Yasumasa Ikeda, Keisuke Ishizawa, Koichiro Tsuchiya, Yoshiro Abe, Ichiro Hashimoto and Toshiaki Tamaki : Topical Application of Nitrosonifedipine, a Novel Radical Scavenger, Ameliorates Ischemic Skin Flap Necrosis in a Mouse Model., Wound Repair and Regeneration, Vol.25, No.2, 217-223, 2017. (要約) Ischemic skin flap necrosis can occur in random pattern flaps. An excess amount of reactive oxygen species is generated and causes necrosis in the ischemic tissue. Nitrosonifedipine (NO-NIF) has been demonstrated to possess potent radical scavenging ability. However, there has been no study on the effects of NO-NIF on ischemic skin flap necrosis. Therefore, they evaluated the potential of NO-NIF in ameliorating ischemic skin flap necrosis in a mouse model. A random pattern skin flap (1.0 × 3.0 cm) was elevated on the dorsum of C57BL/6 mice. NO-NIF was administered by topical injection immediately after surgery and every 24 hours thereafter. Flap survival was evaluated on postoperative day 7. Tissue samples from the skin flaps were harvested on postoperative days 1 and 3 to analyze oxidative stress, apoptosis and endothelial dysfunction. The viable area of the flap in the NO-NIF group was significantly increased (78.30 ± 7.041%) compared with that of the control group (47.77 ± 6.549%, p < 0.01). NO-NIF reduced oxidative stress, apoptosis and endothelial dysfunction, which were evidenced by the decrease of malondialdehyde, p22phox protein expression, number of apoptotic cells, phosphorylated p38 MAPK protein expression, and vascular cell adhesion molecule-1 protein expression while endothelial nitric oxide synthase protein expression was increased. In conclusion, they demonstrated that NO-NIF ameliorated ischemic skin flap necrosis by reducing oxidative stress, apoptosis, and endothelial dysfunction. NO-NIF is considered to be a candidate for the treatment of ischemic flap necrosis. (徳島大学機関リポジトリ) ● Metadata: 110118 (出版サイトへのリンク) ● Publication site (DOI): 10.1111/wrr.12510 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28090711 ● Search Scopus @ Elsevier (PMID): 28090711 ● Search Scopus @ Elsevier (DOI): 10.1111/wrr.12510 (徳島大学機関リポジトリ: 110118, DOI: 10.1111/wrr.12510, PubMed: 28090711)
22.	Masaki Imanishi, Chiba Yoichi, Tomita Noriko, Matsunaga Shinji, Nakagawa Toshitaka, Ueno Masaki, Yamamoto Kazuhiro, Toshiaki Tamaki and Shuhei Tomita : Hypoxia-Inducible Factor-1α in Smooth Muscle Cells Protects Against Aortic Aneurysms-Brief Report., Arteriosclerosis, Thrombosis, and Vascular Biology, Vol.36, No.11, 2158-2162, 2016. (要約) The purpose of this study was to determine the role of smooth muscle cell-derived hypoxia-inducible factor-1α (Hif-1α) in the pathogenesis of aortic aneurysms. Control mice and smooth muscle cell-specific hypoxia-inducible factor-1α-deficient mice were infused with β-aminopropionitrile for 2 weeks and angiotensin II for 6 weeks to induce aortic aneurysm formation. Mutant mice experienced increased levels of aneurysm formation of the thoracic or abdominal aorta with more severe elastin disruption, compared with control mice. Smooth muscle cell-specific hypoxia-inducible factor-1α deficiency did not affect matrix metalloproteinase-2 activity; however, the activity of lysyl oxidase and the levels of tropoelastin mRNA in the angiotensin II- and β-aminopropionitrile-treated aortae, associated with elastin fiber formation, were suppressed. Furthermore, we observed reduced volumes of mature cross-linked elastin in the thoracoabdominal aorta after treatment with angiotensin II and β-aminopropionitrile. Deficiency of smooth muscle cell-derived hypoxia-inducible factor-1α augments aortic aneurysms, accompanied by disruption of elastin fiber formation, but not changes of elastin fiber degradation. (キーワード) Aminopropionitrile / Angiotensin II / Animals / Aorta, Abdominal / Aorta, Thoracic / Aortic Aneurysm, Abdominal / Aortic Aneurysm, Thoracic / Cells, Cultured / Dilatation, Pathologic / Disease Models, Animal / Elastic Tissue / Genetic Predisposition to Disease / Hypoxia-Inducible Factor 1, alpha Subunit / 男性 (male) / Mice, Knockout / Muscle, Smooth, Vascular / Myocytes, Smooth Muscle / Phenotype / Protein-Lysine 6-Oxidase / Tropoelastin / Vascular Remodeling (出版サイトへのリンク) ● Publication site (DOI): 10.1161/ATVBAHA.116.307784 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27562915 ● Summary page in Scopus @ Elsevier: 2-s2.0-84983748456 (DOI: 10.1161/ATVBAHA.116.307784, PubMed: 27562915, Elsevier: Scopus)
23.	Yasumasa Ikeda, Mizuki Imao, Akiho Satoh, Hiroaki Watanabe, Hirofumi Hamano, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Iron-induced skeletal muscle atrophy involves an Akt-forkhead box O3-E3 ubiquitin ligase-dependent pathway, Journal of Trace Elements in Medicine and Biology, Vol.35, No.5, 66-76, 2016. (要約) Skeletal muscle wasting or sarcopenia is a critical health problem. Skeletal muscle atrophy is induced by an excess of iron, which is an essential trace metal for all living organisms. Excessive amounts of iron catalyze the formation of highly toxic hydroxyl radicals via the Fenton reaction. However, the molecular mechanism of iron-induced skeletal muscle atrophy has remained unclear. In this study, 8-weeks-old C57BL6/J mice were divided into 2 groups: vehicle-treated group and the iron-injected group (10 mg iron·day-1·mouse-1) during 2 weeks. Mice in the iron-injected group showed an increase in the iron content of the skeletal muscle and serum and ferritin levels in the muscle, along with reduced skeletal muscle mass. The skeletal muscle showed elevated mRNA expression of the muscle atrophy-related E3 ubiquitin ligases, atrogin-1 and muscle ring finger-1(MuRF1), on days 7 and 14 of iron treatment. Moreover, iron-treated mice showed reduced phosphorylation of Akt and forkhead box O3 (FOXO3a) in skeletal muscles. Inhibition of FOXO3a using siRNA in vitro in C2C12 myotube cells inhibited iron-induced upregulation of atrogin-1 and MuRF1 and reversed the reduction in myotube diameters. Iron-load caused oxidative stress, and an oxidative stress inhibitor abrogated iron-induced muscle atrophy by reactivating the Akt-FOXO3 pathway. Iron-induced skeletal muscle atrophy is suggested to involve the E3 ubiquitin ligase mediated by the reduction of Akt-FOXO3a signaling by oxidative stress. (徳島大学機関リポジトリ) ● Metadata: 113750 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.jtemb.2016.01.011 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27049128 ● Search Scopus @ Elsevier (PMID): 27049128 ● Search Scopus @ Elsevier (DOI): 10.1016/j.jtemb.2016.01.011 (徳島大学機関リポジトリ: 113750, DOI: 10.1016/j.jtemb.2016.01.011, PubMed: 27049128)
24.	Yasumasa Ikeda, Hirofumi Hamano, Akiho Satoh, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Ken-ichi Aihara, Koichiro Tsuchiya and Toshiaki Tamaki : Bilirubin exerts pro-angiogenic effects through an Akt-eNOS-dependent pathway, Hypertension Research, Vol.38, No.11, 733-740, 2015. (要約) Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as antioxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin-treated group). The analysis of laser speckle blood flow demonstrated the enhancement of blood flow recovery in response to ischemia of mice with bilirubin treatment. The density of capillaries was significantly higher in ischemic-adductor muscles of bilirubin-treated mice. The phosphorylated levels of endothelial nitric oxide synthase (eNOS) and Akt were increased in ischemic skeletal muscles of mice with bilirubin treatment compared with vehicle treatment. In in vitro experiments by using human aortic endothelial cells, bilirubin augmented eNOS and Akt phosphorylation, cell proliferation, cell migration and tube formation. These bilirubin actions on endothelial cell activation were inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. In conclusion, bilirubin promotes angiogenesis through endothelial cells activation via Akt-eNOS-dependent manner. (徳島大学機関リポジトリ) ● Metadata: 113751 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/hr.2015.74 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26134126 ● Summary page in Scopus @ Elsevier: 2-s2.0-84946558014 (徳島大学機関リポジトリ: 113751, DOI: 10.1038/hr.2015.74, PubMed: 26134126, Elsevier: Scopus)
25.	Soichiro Tajima, Yasumasa Ikeda, Hideaki Enomoto, Mizuki Imao, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice, European Journal of Nutrition, Vol.54, No.5, 709-719, 2015. (要約) Angiotensin II (ANG II) has been shown to affect iron metabolism through alteration of iron transporters, leading to increased cellular and tissue iron contents. Serum ferritin, a marker of body iron storage, is elevated in various cardiovascular diseases, including hypertension. However, the associated changes in iron absorption and the mechanism underlying increased iron content in a hypertensive state remain unclear. The C57BL6/J mice were treated with ANG II to generate a model of hypertension. Mice were divided into three groups: (1) control, (2) ANG II-treated, and (3) ANG II-treated and ANG II receptor blocker (ARB)-administered (ANG II-ARB) groups. Mice treated with ANG II showed increased serum ferritin levels compared to vehicle-treated control mice. In ANG II-treated mice, duodenal divalent metal transporter-1 and ferroportin (FPN) expression levels were increased and hepatic hepcidin mRNA expression and serum hepcidin concentration were reduced. The mRNA expression of bone morphogenetic protein 6 and CCAAT/enhancer-binding protein alpha, which are regulators of hepcidin, was also down-regulated in the livers of ANG II-treated mice. In terms of tissue iron content, macrophage iron content and renal iron content were increased by ANG II treatment, and these increases were associated with reduced expression of transferrin receptor 1 and FPN and increased expression of ferritin. These changes induced by ANG II treatment were ameliorated by the administration of an ARB. Angiotensin II (ANG II) altered the expression of duodenal iron transporters and reduced hepcidin levels, contributing to the alteration of body iron distribution. (徳島大学機関リポジトリ) ● Metadata: 113753 (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s00394-014-0749-1 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25096756 ● Summary page in Scopus @ Elsevier: 2-s2.0-84937513465 (徳島大学機関リポジトリ: 113753, DOI: 10.1007/s00394-014-0749-1, PubMed: 25096756, Elsevier: Scopus)
26.	Yoshitaka Kihira, Ariunzaya Burentogtokh, Mari Itoh, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : Hypoxia decreases glucagon-like peptide-1 secretion from GLUTag cell line, Biological & Pharmaceutical Bulletin, Vol.38, No.4, 514-521, 2015. (要約) Glucagon-like peptide-1 (GLP-1), an incretin hormone, is secreted from L cells located in the intestinal epithelium. It is known that intestinal oxygen tension is decreased postprandially. In addition, we found that the expression of hypoxia-inducible factor-1α (HIF-1α), which accumulates in cells under hypoxic conditions, was significantly increased in the colons of mice with food intake, indicating that the oxygen concentration is likely reduced in the colon after eating. Therefore, we hypothesized that GLP-1 secretion is affected by oxygen tension. We found that forskolin-stimulated GLP-1 secretion from GLUTag cells, a model of intestinal L cells, is suppressed in hypoxia (1% O2). Forskolin-stimulated elevations of preproglucagon (ppGCG) and proprotein convertase 1/3 (PC1/3) mRNA expression were decreased under hypoxic conditions. The finding that H89, a protein kinase A (PKA) inhibitor, inhibited the forskolin-stimulated increase of ppGCG and PC1/3 indicated that the cAMP-PKA pathway is involved in the hypoxia-induced suppression of the genes. Hypoxia decreased hexokinase 2 mRNA and protein expression and increased lactate dehydrogenase A mRNA and protein expression. Concomitantly, lactate production was increased and ATP production was decreased. Together, the results indicate that hypoxia decreases glucose utilization for ATP production, which probably causes a decrease in cAMP production and in subsequent GLP-1 production. Our findings suggest that the postprandial decrease in oxygen tension in the intestine attenuates GLP-1 secretion. (徳島大学機関リポジトリ) ● Metadata: 109948 (出版サイトへのリンク) ● Publication site (DOI): 10.1248/bpb.b14-00612 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25832631 ● CiNii @ 国立情報学研究所 (CRID): 1390001204631777920 ● Summary page in Scopus @ Elsevier: 2-s2.0-84928951796 (徳島大学機関リポジトリ: 109948, DOI: 10.1248/bpb.b14-00612, PubMed: 25832631, CiNii: 1390001204631777920, Elsevier: Scopus)
27.	Noriko Yamano, Yasumasa Ikeda, Minoru Sakama, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Licht Miyamoto, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : A Long-Term High-Fat Diet Changes Iron Distribution in Body, Increasing Iron Accumulation Specifically in the Mouse Spleen, Journal of Nutritional Science and Vitaminology, Vol.61, No.1, 20-27, 2015. (要約) Although iron is an essential trace metal, its presence in excess causes oxidative stress in the human body. Recent studies have indicated that iron storage is a risk factor for type 2 diabetes mellitus. Dietary iron restriction or iron chelation ameliorates symptoms of type 2 diabetes in mouse models. However, whether iron content in the body changes with the development of diabetes is unknown. Here, we investigated the dynamics of iron accumulation and changes in iron absorption-related genes in mice that developed obesity and diabetes by consuming a high-fat diet (HFD-fed mice). HFD-fed mice (18-20 wk) were compared with control mice for hematologic features, serum ferritin levels, and iron contents in the gastrocnemius muscle, heart, epididymal fat, testis, liver, duodenum, and spleen. In addition, the spleen was examined histologically. Iron absorption-related gene expression in the liver and duodenum was also examined. Hemoglobin and serum ferritin levels were increased in HFD-fed mice. The HFD-fed mice showed iron accumulation in the spleen, but not in the heart or liver. Increased percentages of the splenic red pulp and macrophages were observed in HFD-fed mice and iron accumulation in the spleen was found mainly in the splenic red pulp. The HFD-fed mice also showed decreased iron content in the duodenum. The mRNA expression of divalent metal transporter-1 (DMT-1), an iron absorption-related gene, was elevated in the duodenum of HFD-fed mice. These results indicate that iron accumulation (specifically accumulation in the spleen) is enhanced by the development of type 2 diabetes induced by HFD. (キーワード) iron/spleen/diet / high fat/diabetes mellitus / type 2/DMT1 protein (iron transporter) (出版サイトへのリンク) ● Publication site (DOI): 10.3177/jnsv.61.20 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25994136 ● CiNii @ 国立情報学研究所 (CRID): 1390282681302013696 ● Summary page in Scopus @ Elsevier: 2-s2.0-84929747372 (DOI: 10.3177/jnsv.61.20, PubMed: 25994136, CiNii: 1390282681302013696, Elsevier: Scopus)
28.	Masashi Akaike, Ken-ichi Aihara, Hiroaki Yanagawa, Takashi Iwase, Sumiko Yoshida, Sato Chiho, Saijo Tomoka, Hiroaki Mikasa, Kashiwada Yoshizaki, Yoshihisa Takaishi, Koichiro Tsuchiya, Toshiaki Tamaki, Toshio Matsumoto and Masataka Sata : Efficacy and safety of Citrus sudachi peel in obese adults:A randomized, double-blind, pilot study, Functional Foods in Health and Disease, Vol.4, No.6, 276-284, 2014. (出版サイトへのリンク) ● Publication site (DOI): 10.31989/ffhd.v4i7.5 (文献検索サイトへのリンク) ● Summary page in Scopus @ Elsevier: 2-s2.0-85054855286 (DOI: 10.31989/ffhd.v4i7.5, Elsevier: Scopus)
29.	Masaki Imanishi, Shuhei Tomita, Keisuke Ishizawa, Yoshitaka Kihira, Masaki Ueno, Yuki Izawa-Ishizawa, Yasumasa Ikeda, Noriko Yamano, Koichiro Tsuchiya and Toshiaki Tamaki : Smooth muscle cell specific Hif-1 deficiency suppresses angiotensin II-induced vascular remodeling in mice, Cardiovascular Research, Vol.102, No.3, 460-468, 2014. (要約) Vascular remodelling is mediated by vascular smooth muscle cell (VSMC) proliferation and hypertrophy, both processes of which are linked to medial thickening and fibrosis. Here, we show that hypoxia-inducible factor-1α (Hif-1α) expressed in smooth muscle cells (SMCs) is involved in angiotensin II (Ang II)-induced vascular remodelling in an in vivo model. To clarify the role of Hif-1α in vascular remodelling, we created mice lacking the Hif-1α gene in SMCs (SMKO mice). Ang II infusion induced medial thickening and vascular fibrosis, accompanied by Hif-1α up-regulation, in the aortae of control mice, but not in those of SMKO mice. In accordance with those results, our in vitro studies showed that the deletion of SMC-derived Hif-1α suppressed the Ang II-induced hypertrophy of VSMCs, and our in vivo studies showed that the Ang II-induced expression of fibrosis-related genes in aortae was suppressed by SMC-specific Hif-1α deficiency. In addition, the SMC-specific Hif-1α deficiency suppressed Ang II-induced macrophage infiltration and Ang II-induced expression of inflammation-related genes in aortae. The superoxide production observed in the aortae of control mice with Ang II was suppressed in those of SMKO mice with Ang II, and this finding was consistent with the results of little Ang II-induced c-Src phosphorylation in SMKO mouse aortae. Loss- and gain-of-function analysis in in vitro experiments confirmed that VSMC-derived Hif-1α functions as an intrinsic modulator of vascular remodelling-related gene expression. Our results revealed that SMC-derived Hif-1α is a crucial mediator of Ang II-induced vascular remodelling. (キーワード) Angiotensin II / Animals / Fibrosis / Gene Expression Regulation / Hemodynamics / Hypoxia-Inducible Factor 1, alpha Subunit / Mice / Muscle, Smooth, Vascular / Myocytes, Smooth Muscle / リン酸化 (phosphorylation) / Superoxides / Vascular Remodeling (徳島大学機関リポジトリ) ● Metadata: 106145 (出版サイトへのリンク) ● Publication site (DOI): 10.1093/cvr/cvu061 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24623277 ● Summary page in Scopus @ Elsevier: 2-s2.0-84901457818 (徳島大学機関リポジトリ: 106145, DOI: 10.1093/cvr/cvu061, PubMed: 24623277, Elsevier: Scopus)
30.	Yuko Imamura, Shuhei Tomita, Masaki Imanishi, Yoshitaka Kihira, Yasumasa Ikeda, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : HIF-2α/ARNT complex regulates hair development via induction of p21Waf1/Cip1 and p27Kip1, The FASEB journal, Vol.28, No.6, 2517-2524, 2014. (要約) The hypoxia-inducible factors HIF-1α or HIF-2α form heterodimeric complexes with the aryl hydrocarbon receptor nuclear translocator (ARNT). HIF-1α/ARNT and HIF-2α/ARNT complexes activate hypoxia-inducible genes that play critical roles in angiogenesis, anaerobic metabolism, and other processes in response to O2 deprivation. HIF-2α is known to regulate the function and/or differentiation of stem cells by activating the POU domain transcription factor Oct4; however, the precise underlying mechanism is unknown. This study examined the role of HIF-2α/ARNT in hair development using conditional-knockout mice, in which Arnt was specifically deleted in keratinocytes. In wild-type mice, HIF-2α and ARNT were highly expressed in the precortex above the hair matrix, an area containing differentiating stem cells. An analysis of hair size and type in these mice showed that loss of ARNT decreased the production of zigzag hairs, corresponding to reduced expression of HIF-2α and induction of the mammalian cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27 (Kip1). The results suggest that the HIF-2α/ARNT complex regulates hair follicle differentiation via induction of p21(Waf1/Cip1) and possibly p27(Kip1), as p27(Kip1) expression was not altered in ARNT knockout mice. The findings provide insight into a possible mechanism underlying hair growth disorders and can be useful for future studies on hair follicle response to insults, such as chemotherapy and ionizing radiation.-Imamura, Y., Tomita, S., Imanishi, M., Kihira, Y., Ikeda, Y., Ishizawa, K., Tsuchiya, K., Tamaki, T. HIF-2α/ARNT complex regulates hair development via induction of p21(Waf1/Cip1) and p27(Kip1). (キーワード) Animals / Aryl Hydrocarbon Receptor Nuclear Translocator / Basic Helix-Loop-Helix Transcription Factors / 細胞分化 (cell differentiation) / Cells, Cultured / Cyclin-Dependent Kinase Inhibitor p21 / Cyclin-Dependent Kinase Inhibitor p27 / Hair / Hair Follicle / Hypoxia-Inducible Factor 1, alpha Subunit / Keratinocytes / Mice / ノックアウトマウス (knockout mice) (出版サイトへのリンク) ● Publication site (DOI): 10.1096/fj.13-244079 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24599965 ● Summary page in Scopus @ Elsevier: 2-s2.0-84901845393 (DOI: 10.1096/fj.13-244079, PubMed: 24599965, Elsevier: Scopus)
31.	S Hayashi, Hirotsugu Yamada, Mika Bando, Junko Hotsuchi, Takayuki Ise, Koji Yamaguchi, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki, Toshiaki Tamaki and Masataka Sata : Augmentation Index does not Reflect the Risk of Coronary Artery Disease in Elderly Patients., Circulation Journal, Vol.78, No.5, 1176-1182, 2014. (要約) BACKGROUND: Augmentation index (AI) has been used as a clinical index of arterial stiffness and has been reported to be an independent predictor of cardiovascular events, but some investigators have reported that AI is not a useful marker to identify coronary artery disease (CAD) in elderly patients. The majority of CAD patients are elderly people, therefore the aim of this study was to examine whether AI is a useful marker to identify the risk of CAD.METHODS AND RESULTS: A total of 120 patients (69±10 years of age; 83 male) who underwent cardiac catheterization for suspected CAD were enrolled. Invasive central blood pressure (BP) was measured using a fluid-filled catheter. Non-invasive AI was calculated by the SphygmoCor (AtCor Medical) system at the end of catheterization. Subjects consisted of 99 patients with CAD and 21 patients without CAD. There was no significant difference in AI between the CAD and the non-CAD groups (24±10 vs. 24±14%). Non-invasive systolic central BP was lower than the invasive systolic central BP (115±18 vs. 130±23 mmHg, P<0.001) in all patients. Non-invasive diastolic central BP was greater than the invasive diastolic central BP (67±10 vs. 63±10 mmHg, P<0.001).CONCLUSIONS: In elderly patients, AI may not be a useful marker to identify CAD (キーワード) Arterial stiffness / Augmentation index / Central blood pressure / Coronary artery disease (徳島大学機関リポジトリ) ● Metadata: 106070 (出版サイトへのリンク) ● Publication site (DOI): 10.1253/circj.CJ-13-1422 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24562676 ● CiNii @ 国立情報学研究所 (CRID): 1390001205107150592 ● Summary page in Scopus @ Elsevier: 2-s2.0-84899659435 (徳島大学機関リポジトリ: 106070, DOI: 10.1253/circj.CJ-13-1422, PubMed: 24562676, CiNii: 1390001205107150592, Elsevier: Scopus)
32.	Atsushi Morimoto, Shuhei Tomita, Masaki Imanishi, Go Shioi, Yoshitaka Kihira, Yuki Izawa-Ishizawa, Mitsuru Takaku, Ichiro Hashimoto, Yasumasa Ikeda, Hideki Nakanishi and Toshiaki Tamaki : Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap Survival., Plastic and Reconstructive Surgery. Global Open, Vol.2, No.4, e132, 2014. (要約) Specific overexpression of HIF-2 in ECs promoted vascularization and enhanced skin flap survival in vivo in a mouse model. (徳島大学機関リポジトリ) ● Metadata: 106138 (出版サイトへのリンク) ● Publication site (DOI): 10.1097/GOX.0000000000000083 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25289325 ● Summary page in Scopus @ Elsevier: 2-s2.0-84897362750 (徳島大学機関リポジトリ: 106138, DOI: 10.1097/GOX.0000000000000083, PubMed: 25289325, Elsevier: Scopus)
33.	Yoshitaka Kihira, Mariko Miyake, Manami Hirata, Yoji Hoshina, Kana Kato, Hitoshi Shirakawa, Hiroshi Sakaue, Noriko Yamano, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya, Toshiaki Tamaki and Shuhei Tomita : Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation., PLoS ONE, Vol.9, No.4, e93856, 2014. (要約) It is known that obese adipose tissues are hypoxic and express hypoxia-inducible factor (HIF)-1α. Although some studies have shown that the expression of HIF-1α in adipocytes induces glucose intolerance, the mechanisms are still not clear. In this study, we examined its effects on the development of type 2 diabetes by using adipocyte-specific HIF-1α knockout (ahKO) mice. ahKO mice showed improved glucose tolerance compared with wild type (WT) mice. Macrophage infiltration and mRNA levels of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor α (TNFα) were decreased in the epididymal adipose tissues of high fat diet induced obese ahKO mice. The results indicated that the obesity-induced adipose tissue inflammation was suppressed in ahKO mice. In addition, in the ahKO mice, serum insulin levels were increased under the free-feeding but not the fasting condition, indicating that postprandial insulin secretion was enhanced. Serum glucagon-like peptide-1 (GLP-1) levels were also increased in the ahKO mice. Interestingly, adiponectin, whose serum levels were increased in the obese ahKO mice compared with the obese WT mice, stimulated GLP-1 secretion from cultured intestinal L cells. Therefore, insulin secretion may have been enhanced through the adiponectin-GLP-1 pathway in the ahKO mice. Our results suggest that the deletion of HIF-1α in adipocytes improves glucose tolerance by enhancing insulin secretion through the GLP-1 pathway and by reducing macrophage infiltration and inflammation in adipose tissue. (キーワード) Adipocytes / Animals / Blotting, Western / Chemokine CCL2 / DNA Primers / Diabetes Mellitus, Type 2 / Gene Deletion / Glucagon-Like Peptide 1 / Glucose Tolerance Test / Hypoxia-Inducible Factor 1, alpha Subunit / Immunohistochemistry / Insulin / Mice / Mice, Knockout / Real-Time Polymerase Chain Reaction / Tumor Necrosis Factor-alpha (出版サイトへのリンク) ● Publication site (DOI): 10.1371/journal.pone.0093856 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24705496 ● Summary page in Scopus @ Elsevier: 2-s2.0-84899440448 (DOI: 10.1371/journal.pone.0093856, PubMed: 24705496, Elsevier: Scopus)
34.	Yasumasa Ikeda, Iori Ozono, Soichro Tajima, Mizuki Imao, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction, PLoS ONE, Vol.9, No.2, e89355, 2014. (要約) Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases (CKD). Although several mechanisms underlying renal fibrosis and candidate drugs for its treatment have been identified, the effect of iron chelator on renal fibrosis remains unclear. In the present study, we examined the effect of an iron chelator, deferoxamine (DFO), on renal fibrosis in mice with surgically induced unilateral ureter obstruction (UUO). Mice were divided into 4 groups: UUO with vehicle, UUO with DFO, sham with vehicle, and sham with DFO. One week after surgery, augmented renal tubulointerstitial fibrosis and the expression of collagen I, III, and IV increased in mice with UUO; these changes were suppressed by DFO treatment. Similarly, UUO-induced macrophage infiltration of renal interstitial tubules was reduced in UUO mice treated with DFO. UUO-induced expression of inflammatory cytokines and extracellular matrix proteins was abrogated by DFO treatment. DFO inhibited the activation of the transforming growth factor-β1 (TGF-β1)-Smad3 pathway in UUO mice. UUO-induced NADPH oxidase activity and p22(phox) expression were attenuated by DFO. In the kidneys of UUO mice, divalent metal transporter 1, ferroportin, and ferritin expression was higher and transferrin receptor expression was lower than in sham-operated mice. Increased renal iron content was observed in UUO mice, which was reduced by DFO treatment. These results suggest that iron reduction by DFO prevents renal tubulointerstitial fibrosis by regulating TGF-β-Smad signaling, oxidative stress, and inflammatory responses. (徳島大学機関リポジトリ) ● Metadata: 113752 (出版サイトへのリンク) ● Publication site (DOI): 10.1371/journal.pone.0089355 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24586712 ● Summary page in Scopus @ Elsevier: 2-s2.0-84897786390 (徳島大学機関リポジトリ: 113752, DOI: 10.1371/journal.pone.0089355, PubMed: 24586712, Elsevier: Scopus)
35.	Keisuke Ishizawa, Yuki Izawa-Ishizawa, Noriko Yamano, Maki Urushihara, Takumi Sakurada, Masaki Imanishi, Shoko Fujii, Asami Nuno, Licht Miyamoto, Yoshitaka Kihira, Yasumasa Ikeda, Shoji Kagami, Hiroyuki Kobori, Koichiro Tsuchiya and Toshiaki Tamaki : Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects, PLoS ONE, Vol.9, No.1, e86335, 2014. (要約) Diabetic nephropathy (DN) is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF) is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice), NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM)-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS) knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT) excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects. (キーワード) Animals / Antioxidants / Cell Line / Diabetic Nephropathies / Humans / Male / Mice / Mice, Inbred C57BL / ノックアウトマウス (knockout mice) / Nifedipine / Nitric Oxide Synthase Type III / Nitroso Compounds / 酸化ストレス (oxidative stress) (出版サイトへのリンク) ● Publication site (DOI): 10.1371/journal.pone.0086335 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24489716 ● Summary page in Scopus @ Elsevier: 2-s2.0-84900332178 (DOI: 10.1371/journal.pone.0086335, PubMed: 24489716, Elsevier: Scopus)
36.	Hirose Kayo, Hirose Masao, Katsuya Tanaka, Shinji Kawahito, Toshiaki Tamaki and Shuzo Oshita : Perioperative management of severe anorexia nervosa., British Journal of Anaesthesia, Vol.112, No.2, 246-254, 2013. (要約) As the prevalence of anorexia nervosa (AN) increased, surgery in severe AN patients also increased in the 2000s. We experienced a surgical case of a patient with severe AN, showing an extremely low BMI of 8.6 kg m(-2). We investigated the problems associated with this case and propose criteria to manage severe AN. We endeavour to report on the perioperative management of rare and severe symptoms and surgical indications of severely malnourished patients. All published reports were identified through comprehensive searches using PubMed, BioMedLib, and the Japan Medical Abstracts Society with the following terms and keywords: 'anorexia nervosa', 'eating disorder', 'hypoglycaemia', 'leucocytopaenia', 'gelatinous bone marrow', 'surgery', and 'operation'. In cases of AN with a BMI under 13 kg m(-2), marked hypoglycaemia, leucocytopaenia <3.0×10(9) litre(-1), or both, potentially fatal complications frequently occur. Accordingly, patients need strict nutritional support to avoid re-feeding syndrome until surgery. During the course of anaesthesia, careless loading of glucose or catecholamine may lead to disturbance of electrolytes or fatal arrhythmia. Intensive care and early feeding as soon as possible after surgery are important to prevent surgical site infection. Although not many perioperative cases of AN have been reported, clinicians must be aware of the danger and the causes of mortality in critical cases. Thus, the decision to undertake surgery must be taken carefully and close perioperative coordination among physicians, surgeons, psychiatrists, anaesthesiologists, and intensivists is essential. (キーワード) Adult / 麻酔 (anesthesia) / Anorexia Nervosa / Female / Fractures, Bone / Heart Diseases / Humans / Hypoglycemia / 低体温 (hypothermia) / Intraoperative Complications / Male / Malnutrition / Nutritional Support / Perioperative Care / Postoperative Complications / Surgical Procedures, Operative / Surgical Wound Infection (出版サイトへのリンク) ● Publication site (DOI): 10.1093/bja/aet415 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24366724 ● Search Scopus @ Elsevier (PMID): 24366724 ● Search Scopus @ Elsevier (DOI): 10.1093/bja/aet415 (DOI: 10.1093/bja/aet415, PubMed: 24366724)
37.	Taisuke Nakayama, Hirotsugu Kurobe, Noriko Sugasawa, Hajime Kinoshita, Mayuko Higashida, Yuki Matsuoka, Yasushi Yoshida, Yoichiro Hirata, Mie Sakata, Mark Maxfield, Yousuke Takahama, Masataka Sata, Toshiaki Tamaki, Tetsuya Kitagawa and Shuhei Tomita : Role of macrophage-derived Hypoxia-Inducible Factor (HIF)-1 as a mediator of vascular remodeling, Cardiovascular Research, Vol.99, No.4, 705-715, 2013. (要約) Excessive vascular remodelling leads to progression of a wide range of vasculopathies, and the immune response to intimal injuries is crucial in this process. This vascular remodelling occurs in the hypoxic microenvironment and is closely related to the immune system. Macrophages play a key role in immunological-cell-mediated arterial remodelling. In this study, we clarified the role of macrophage-derived hypoxia-inducible factor (HIF-1α) in vascular remodelling. Wire-induced femoral arterial injury was inflicted in mice lacking the macrophage-specific HIF-1α gene and in their wild-type counterparts. The mutant mice showed both suppressed wire-induced neointimal thickening and decreased infiltration of inflammatory cells in the adventitia, compared with wild-type mice. Studies to clarify the mechanism of restrained vascular remodelling in the mutant mice revealed decreased production of pro-inflammatory cytokines by the activated macrophages and suppressed macrophage migration activity in the mutant mice. Gene expressions of the HIF-1α-deficient macrophages positively correlated with the phenotypic profile of M2 macrophages and negatively correlated with that of M1 macrophages. Our results show that HIF-1α in macrophages plays a crucial role in promoting vascular inflammation and remodelling. As decreasing HIF-1α activity in macrophages may prevent the progression of vascular remodelling, HIF-1α may be a possible therapeutic target in vascular diseases. (キーワード) Animals / Blood Vessels / Cell Movement / HMGB1 Protein / Hypoxia-Inducible Factor 1, alpha Subunit / Interleukin-6 / Macrophages / Mice / Mice, Inbred C57BL / Phenotype / Tumor Necrosis Factor-alpha (徳島大学機関リポジトリ) ● Metadata: 105898 (出版サイトへのリンク) ● Publication site (DOI): 10.1093/cvr/cvt146 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23752975 ● Search Scopus @ Elsevier (PMID): 23752975 ● Search Scopus @ Elsevier (DOI): 10.1093/cvr/cvt146 (徳島大学機関リポジトリ: 105898, DOI: 10.1093/cvr/cvt146, PubMed: 23752975)
38.	Yasumasa Ikeda, Hideaki Enomoto, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Dietary iron restriction inhibits progression of diabetic nephropathy in db/db mice., American Journal of Physiology, Renal Physiology, Vol.304, No.7, F1028-F1036, 2013. (要約) Excess iron causes oxidative stress through hydroxyl-radical production via Fenton/Haber-Weiss reactions. Recently, body iron reduction has been found to ameliorate diabetes. In the present study, we examined the protective effect of dietary iron restriction against diabetic nephropathy in the db/db mouse model of diabetic nephropathy using db/m mice as controls. The db/db mice were divided into 2 groups and fed a normal diet (ND) or a low iron diet (LID). Increasing urinary albumin excretion was observed in the ND db/db mice, but this was suppressed in db/db mice with LID. Histologically, the db/db mice in the ND group had increased glomerular volume and mesangial area compared to the LID group. Augmented deposition of extracellular matrices was decreased in db/db mice with LID. In terms of oxidative stress, increased superoxide production observed in the kidneys of the ND db/db mice was diminished in the LID group. NADPH oxidase activity and renal expression of NADPH oxidase components p22(phox) and NOX4 were augmented in the ND group, and this was abolished by LID. There were no differences in expression of renal iron importers, transferrin receptor, or divalent metal transporter-1 between db/m mice and db/db mice. The level of ferroportin, an iron exporter, increased in the kidneys of the db/db mice. Urinary iron excretion was significantly higher in ND db/db mice and was reduced in the LID group. These findings suggest that dietary iron restriction exerts a preventive effect on the progression of diabetic nephropathy partly due to the reduction of oxidative stress. (出版サイトへのリンク) ● Publication site (DOI): 10.1152/ajprenal.00473.2012 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23389454 ● Search Scopus @ Elsevier (PMID): 23389454 ● Search Scopus @ Elsevier (DOI): 10.1152/ajprenal.00473.2012 (DOI: 10.1152/ajprenal.00473.2012, PubMed: 23389454)
39.	Yasumasa Ikeda, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Sumiko Yoshida, Ken-ichi Aihara, Koichiro Tsuchiya and Toshiaki Tamaki : Bovine milk-derived lactoferrin exerts proangiogenic effects in an Src-Akt-eNOS-dependent manner in response to ischemia, Journal of Cardiovascular Pharmacology, Vol.61, No.5, 423-429, 2013. (要約) Lactoferrin (LF) exerts a variety of biological effects, including the promotion of angiogenesis by increasing the expression of angiogenesis-related genes and reducing blood pressure via a nitric oxide-dependent mechanism. In this study, we investigated the effects of LF on angiogenesis using C57BL/6J mice that received daily unilateral treatment with or without bovine milk-derived LF (bLF) after unilateral hindlimb surgery. The analysis of laser speckle blood flow showed that bLF treatment promoted blood flow recovery in response to ischemic hindlimb. The capillary density of ischemic adductor muscles and the phosphorylation of Src, Akt, and endothelial nitric oxide synthase (eNOS) were also significantly higher in bLF-treated mice than in vehicle-treated mice. Furthermore, bLF increased the phosphorylation levels of Src, Akt, and eNOS in in vitro experiments using human aortic endothelial cells. The action of bLF on eNOS phosphorylation was abolished by both LY294002, a phosphatidylinositol 3-kinase inhibitor, and 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo [3,4-d]pyrimidine (PP2), an Src inhibitor. Similarly, bLF-induced acceleration of tube formation, cell proliferation, and cell migration in human aortic endothelial cells were inhibited by LY294002 or PP2. Thus, bLF promotes vascular endothelial cell function via an Src Akt eNOS-dependent pathway, thereby contributing to revascularization in response to ischemia. (キーワード) Animals / Aorta / Cell Movement / Cell Proliferation / Cells, Cultured / Endothelial Cells / Endothelium, Vascular / Enzyme Activation / Hindlimb / Humans / Ischemia / Lactoferrin / Laser-Doppler Flowmetry / Mice / Mice, Inbred C57BL / Milk / Neovascularization, Physiologic / Nitric Oxide Synthase Type III / Phosphorylation / Proto-Oncogene Proteins c-akt / Reperfusion Injury / Signal Transduction / src-Family Kinases (徳島大学機関リポジトリ) ● Metadata: 113754 (出版サイトへのリンク) ● Publication site (DOI): 10.1097/FJC.0b013e318287d526 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23364610 ● Search Scopus @ Elsevier (PMID): 23364610 ● Search Scopus @ Elsevier (DOI): 10.1097/FJC.0b013e318287d526 (徳島大学機関リポジトリ: 113754, DOI: 10.1097/FJC.0b013e318287d526, PubMed: 23364610)
40.	Takumi Sakurada, Keisuke Ishizawa, Masaki Imanishi, Yuki Izawa-Ishizawa, Shoko Fujii, Erika Tominaga, Teppei Tsuneishi, Yuya Horinouchi, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Ken-ichi Aihara, Kazuo Minakuchi, Koichiro Tsuchiya and Toshiaki Tamaki : Nitrosonifedipine ameliorates angiotensin II-induced vascular remodeling via antioxidative effects, Naunyn-Schmiedeberg's Archives of Pharmacology, Vol.386, No.1, 29-39, 2013. (要約) Nifedipine is unstable under light and decomposes to a stable nitroso analog, nitrosonifedipine (NO-NIF). The ability of NO-NIF to block calcium channels is quite weak compared with that of nifedipine. Recently, we have demonstrated that NO-NIF reacts with unsaturated fatty acid leading to generate NO-NIF radical, which acquires radical scavenging activity. However, the effects of NO-NIF on the pathogenesis related with oxidative stress, such as atherosclerosis and hypertension, are unclear. In this study, we investigated the effects of NO-NIF on angiotensin II (Ang II)-induced vascular remodeling. Ang II-induced thickening and fibrosis of aorta were inhibited by NO-NIF in mice. NO-NIF decreased reactive oxygen species (ROS) in the aorta and urinary 8-hydroxy-20-deoxyguanosine. Ang II-stimulated mRNA expressions of p22(phox), CD68, F4/80, monocyte chemoattractant protein-1, and collagen I in the aorta were inhibited by NO-NIF. Moreover, NO-NIF inhibited Ang II-induced cell migration and proliferation of vascular smooth muscle cells (VSMCs). NO-NIF reduced Ang II-induced ROS to the control level detected by dihydroethidium staining and lucigenin chemiluminescence assay in VSMCs. NO-NIF suppressed phosphorylations of Akt and epidermal growth factor receptor induced by Ang II. However, NO-NIF had no effects on intracellular Ca(2+) increase and protein kinase C-δ phosphorylation induced by Ang II in VSMCs. The electron paramagnetic resonance spectra indicated the continuous generation of NO-NIF radical of reaction with cultured VSMCs. These findings suggest that NO-NIF improves Ang II-induced vascular remodeling via the attenuation of oxidative stress. (キーワード) Angiotensin II / Animals / Antioxidants / Aorta, Thoracic / カルシウム (calcium) / Cell Movement / Cell Proliferation / Fibrosis / Male / Mice / Mice, Inbred C57BL / Muscle, Smooth, Vascular / Nifedipine / Nitroso Compounds / 酸化ストレス (oxidative stress) / Rats / 活性酸素 (reactive oxygen species) (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s00210-012-0810-7 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23149861 ● Summary page in Scopus @ Elsevier: 2-s2.0-84872316103 (DOI: 10.1007/s00210-012-0810-7, PubMed: 23149861, Elsevier: Scopus)
41.	Yuki Izawa-Ishizawa, Keisuke Ishizawa, Takumi Sakurada, Masaki Imanishi, Licht Miyamoto, Shoko Fujii, Hironori Taira, Yoshitaka Kihira, Yasumasa Ikeda, Shuichi Hamano, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Angiotensin II receptor blocker improves tumor necrosis factor-α-induced cytotoxicity via antioxidative effect in human glomerular endothelial cells, Pharmacology, Vol.90, No.5-6, 324-331, 2012. (要約) Tumor necrosis factor-α (TNF-α) is known to involve the progression of renal dysfunction through its cytotoxicity and proinflammatory effects such as the induction of intercellular adhesion molecule (ICAM)-1 expression in vascular endothelial cells (ECs). Olmesartan, one of the angiotensin II type 1 receptor blockers (ARBs), has been reported to show protective effects on injured ECs by some causal factors of renal disorder other than angiotensin II. However, the effects of olmesartan on TNF-α-induced glomerular EC damage have not been investigated. In the present study, we investigated the effects of RNH-6270, an active metabolite of olmesartan, on TNF-α-induced human glomerular EC (HGEC) damage to clarify the renoprotective mechanisms of ARBs. Cultured HGECs were stimulated by TNF-α, and then cell viability and cytotoxicity were measured by MTT assay and lactate dehydrogenase release assay, respectively. TNF-α-induced oxidative stress was estimated by dihydroethidium assay and lucigenin chemiluminescence assay. ICAM-1 expression and the phosphorylations of mitogen-activated protein kinases were measured using Western blotting assay. RNH-6270 suppressed cell death and the increase in ICAM-1 expression induced by TNF-α via the inhibition of reactive oxygen species in HGECs. Our findings suggested that olmesartan might have protective effects against TNF-α-induced glomerular EC dysfunction. (キーワード) Angiotensin II Type 1 Receptor Blockers / アポトーシス (apoptosis) / Cell Survival / Cells, Cultured / Endothelial Cells / Humans / Imidazoles / Intercellular Adhesion Molecule-1 / Kidney Glomerulus / 活性酸素 (reactive oxygen species) / Tetrazoles / Tumor Necrosis Factor-alpha (出版サイトへのリンク) ● Publication site (DOI): 10.1159/000343244 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23052181 ● Summary page in Scopus @ Elsevier: 2-s2.0-84867214872 (DOI: 10.1159/000343244, PubMed: 23052181, Elsevier: Scopus)
42.	Yasumasa Ikeda, Ken-ichi Aihara, Sumiko Yoshida, Takashi Iwase, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya, Masataka Sata, Masashi Akaike, Shigeaki Kato, Toshio Matsumoto and Toshiaki Tamaki : Heparin cofactor II, a serine protease inhibitor, promotes angiogenesis via activation of the AMP-activated protein kinase-endothelial nitric-oxide synthase signaling pathway, The Journal of Biological Chemistry, Vol.287, No.41, 34256-34263, 2012. (要約) We previously clarified that heparin cofactor II (HCII), a serine proteinase inhibitor, exerts various protective actions on cardiovascular diseases in both experimental and clinical studies. In the present study, we aimed to clarify whether HCII participates in the regulation of angiogenesis. Male heterozygous HCII-deficient (HCII(+/-)) mice and male littermate wild-type (HCII(+/+)) mice at the age of 12-16 weeks were subjected to unilateral hindlimb ligation surgery. Laser speckle blood flow analysis showed that blood flow recovery in response to hindlimb ischemia was delayed in HCII(+/-) mice compared with that in HCII(+/+) mice. Capillary number, arteriole number, and endothelial nitric-oxide synthase (eNOS), AMP-activated protein kinase (AMPK), and liver kinase B1 (LKB1) phosphorylation in ischemic muscles were decreased in HCII(+/-) mice. Human purified HCII (h-HCII) administration almost restored blood flow recovery, capillary density, and arteriole number as well as phosphorylation levels of eNOS, AMPK, and LKB1 in ischemic muscles of HCII(+/-) mice. Although treatment with h-HCII increased phosphorylation levels of eNOS, AMPK, and LKB1 in human aortic endothelial cells (HAECs), the h-HCII-induced eNOS phosphorylation was abolished by compound C, an AMPK inhibitor, and by AMPK siRNA. In a similar fashion, tube formation, proliferation, and migration of HAECs were also promoted by h-HCII treatment and were abrogated by pretreatment with compound C. HCII potentiates the activation of vascular endothelial cells and the promotion of angiogenesis in response to hindlimb ischemia via an AMPK-eNOS signaling pathway. These findings suggest that HCII is a novel therapeutic target for treatment of patients with peripheral circulation insufficiency. (キーワード) Heparin cofactor II (HCII) / vascular endothelial cells / 血管新生 (angiogenesis) (出版サイトへのリンク) ● Publication site (DOI): 10.1074/jbc.M112.353532 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22904320 ● Search Scopus @ Elsevier (PMID): 22904320 ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M112.353532 (DOI: 10.1074/jbc.M112.353532, PubMed: 22904320)
43.	Mitsuru Takaku, Shuhei Tomita, Hirotsugu Kurobe, Yoshitaka Kihira, Atsushi Morimoto, Mayuko Higashida, Yasumasa Ikeda, Akira Ushiyama, Ichiro Hashimoto, Hideki Nakanishi and Toshiaki Tamaki : Systemic Preconditioning by a Prolyl Hydroxylase Inhibitor Promotes Prevention of Skin Flap Necrosis via HIF-1-Induced Bone Marrow-Derived Cells., PLoS ONE, Vol.7, No.8, 2012. (要約) We demonstrated that transient activation of the HIF signaling pathway by a single systemic DMOG treatment upregulates not only anti-apoptotic pathways but also enhances neovascularization with concomitant increase in the numbers of bone marrow-derived progenitor cells. (徳島大学機関リポジトリ) ● Metadata: 105965 (出版サイトへのリンク) ● Publication site (DOI): 10.1371/journal.pone.0042964 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22880134 ● Search Scopus @ Elsevier (PMID): 22880134 ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0042964 (徳島大学機関リポジトリ: 105965, DOI: 10.1371/journal.pone.0042964, PubMed: 22880134)
44.	Yasumasa Ikeda, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Estrogen regulates hepcidin expression via GPR30-BMP6-dependent signaling in hepatocytes, PLoS ONE, Vol.7, No.7, e40465, 2012. (要約) Hepcidin, a liver-derived iron regulatory protein, plays a crucial role in iron metabolism. It is known that gender differences exist with respect to iron storage in the body; however, the effects of sex steroid hormones on iron metabolism are not completely understood. We focused on the effects of the female sex hormone estrogen on hepcidin expression. First, ovariectomized (OVX) and sham-operated mice were employed to investigate the effects of estrogen on hepcidin expression in an in vivo study. Hepcidin expression was decreased in the livers of OVX mice compared to the sham-operated mice. In OVX mice, bone morphologic protein-6 (BMP6), a regulator of hepcidin, was also found to be downregulated in the liver, whereas ferroportin (FPN), an iron export protein, was upregulated in the duodenum. Both serum and liver iron concentrations were elevated in OVX mice relative to their concentrations in sham-operated mice. In in vitro studies, 17β-estradiol (E(2)) increased the mRNA expression of hepcidin in HepG2 cells in a concentration-dependent manner. E(2)-induced hepatic hepcidin upregulation was not inhibited by ICI 182720, an inhibitor of the estrogen receptor; instead, hepcidin expression was increased by ICI 182720. E(2) and ICI 182720 exhibit agonist actions with G-protein coupled receptor 30 (GPR30), the 7-transmembrane estrogen receptor. G1, a GPR30 agonist, upregulated hepcidin expression, and GPR30 siRNA treatment abolished E(2)-induced hepcidin expression. BMP6 expression induced by E(2) was abolished by GPR30 silencing. Finally, both E(2) and G1 supplementation restored reduced hepatic hepcidin and BMP6 expression and reversed the augmentation of duodenal FPN expression in the OVX mice. In contrast, serum hepcidin was elevated in OVX mice, which was reversed in these mice with E(2) and G1. Thus, estrogen is involved in hepcidin expression via a GPR30-BMP6-dependent mechanism, providing new insight into the role of estrogen in iron metabolism. (出版サイトへのリンク) ● Publication site (DOI): 10.1371/journal.pone.0040465 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22792339 ● Summary page in Scopus @ Elsevier: 2-s2.0-84863827034 (DOI: 10.1371/journal.pone.0040465, PubMed: 22792339, Elsevier: Scopus)
45.	Soichiro Tajima, Yasumasa Ikeda, Kaori Sawada, Noriko Yamano, Yuya Horinouchi, Yoshitaka Kihira, Keisuke Ishizawa, Yuki Izawa-Ishizawa, Kazuyoshi Kawazoe, Shuhei Tomita, Kazuo Minakuchi, Koichiro Tsuchiya and Toshiaki Tamaki : Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice., American Journal of Physiology, Endocrinology and Metabolism, Vol.302, No.1, E77-86, 2012. (要約) Iron is an essential trace metal for most organisms. However, excess iron causes oxidative stress through production of highly toxic hydroxyl radicals via the Fenton/Haber-Weiss reaction. Iron storage in the body is reported to be associated with fat accumulation and type 2 diabetes mellitus. We investigated the role of iron in adiposity by using KKAy mice and obese and diabetic model mice. Eight-week-old KKAy mice were divided into two groups and treated with deferoxamine (DFO), an iron chelator agent, or a vehicle for 2 wk. DFO treatment diminished fat iron concentration and serum ferritin levels in KKAy mice. Fat weight and adipocyte size were reduced significantly in DFO-treated mice compared with vehicle-treated mice. Macrophage infiltration into fat was also decreased in DFO-treated mice compared with vehicle-treated mice. Superoxide production and NADPH oxidase activity in fat, as well as urinary 8-hydroxy-2'-deoxyguanosine excretion, were decreased in KKAy mice after DFO treatment while p22(phox) expression in adipose tissue was diminished in such mice. Ferritin expression in the fat of DFO-treated KKAy mice was decreased. In addition, F4/80-positive cells also presented through both p22(phox) and ferritin expression. The mRNA expression levels of inflammatory cytokines were also reduced in fat tissue of DFO-treated mice. These findings suggest that reduction of iron levels ameliorates adipocyte hypertrophy via suppression of oxidative stress, inflammatory cytokines, and macrophage infiltration, thereby breaking a vicious cycle in obesity. (キーワード) 鉄 (ferrum) / 酸化ストレス (oxidative stress) / 肥満症 (obesity) (出版サイトへのリンク) ● Publication site (DOI): 10.1152/ajpendo.00033.2011 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21917632 ● Search Scopus @ Elsevier (PMID): 21917632 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpendo.00033.2011 (DOI: 10.1152/ajpendo.00033.2011, PubMed: 21917632)
46.	Yoshitaka Kihira, Noriko Yamano, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya, Toshiaki Tamaki and Shuhei Tomita : Basic fibroblast growth factor regulates glucose metabolism through glucose transporter 1 induced by hypoxia-inducible factor-1α in adipocytes, The International Journal of Biochemistry & Cell Biology, Vol.43, No.11, 1602-1611, 2011. (要約) Hypoxia-inducible factor-1 (HIF-1), which is a transcription factor that enhances glycolysis in cells in response to hypoxia, is induced in hypertrophied adipocytes in obesity. Recent studies have shown that growth factors are able to induce HIF-1 by mechanisms independent of hypoxia. Since basic fibroblast growth factor (bFGF), an angiogenic factor, is concentrated in expanding adipose tissue, the possible effects of bFGF on regulation of HIF-1 in adipocytes were investigated. Treatment of differentiated 3T3-L1 adipocytes with bFGF induced HIF-1. Concomitantly, glucose transporter 1 (GLUT1), which is a target gene of HIF-1, was induced at both mRNA and protein levels and was translocated to the plasma membrane. A chromatin immunoprecipitation assay and an RNA interference study indicated that bFGF-induced HIF-1 directly upregulates GLUT1. In addition, it was observed that bFGF increases lactate production of adipocytes. This result indicates that bFGF reprograms the metabolism toward glycolysis. Intraperitoneal injection of bFGF into mice upregulated HIF-1 and GLUT1 in adipose tissues, suggesting that bFGF regulates the metabolism of adipocytes via HIF-1-GLUT1 regulation in vivo. We also found that bFGF inhibits insulin-induced phosphorylation of insulin receptor substrate-1 and Akt, suggesting that bFGF attenuates the insulin signal in adipocytes. Taken together, the findings suggest that bFGF has a harmful effect on the development of type 2 diabetes through metabolism reprogramming and attenuation of the insulin signal. (キーワード) 3T3-L1 Cells / Adipocytes / Animals / Anoxia / Diabetes Mellitus, Type 2 / Fibroblast Growth Factor 2 / Glucose / Glucose Transporter Type 1 / Glycolysis / Hypoxia-Inducible Factor 1, alpha Subunit / Injections, Intraperitoneal / Insulin / Insulin Receptor Substrate Proteins / Male / Mice / Obesity / Phosphorylation / Proto-Oncogene Proteins c-akt / Signal Transduction / Transcriptional Activation / Up-Regulation (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.biocel.2011.07.009 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21810481 ● Search Scopus @ Elsevier (PMID): 21810481 ● Search Scopus @ Elsevier (DOI): 10.1016/j.biocel.2011.07.009 (DOI: 10.1016/j.biocel.2011.07.009, PubMed: 21810481)
47.	Shuhei Tomita, Yoshitaka Kihira, Masaki Imanishi, Yayoi Fukuhara, Yuko Imamura, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : Pathophysiological Response to Hypoxia From the Molecular Mechanisms of Malady to Drug Discovery: Inflammatory Responses of Hypoxia-Inducible Factor 1 (HIF-1) in T Cells Observed in Development of Vascular Remodeling, Journal of Pharmacological Sciences, Vol.115, No.4, 433-439, 2011. (要約) Recent studies have shown that the cellular immune response to the hypoxic microenvironment constructed by vascular remodeling development modulates the resulting pathologic alterations. A major mechanism mediating adaptive responses to reduced oxygen availability is the regulation of transcription by hypoxia-inducible factor 1 (HIF-1). Impairment of HIF-1-dependent inflammatory responses in T cells causes an augmented vascular remodeling induced by arterial injury, which is shown as prominent neointimal hyperplasia and increase in infiltration of inflammatory cells at the adventitia in mice lacking Hif-1α specifically in T cells. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice have shown enhanced production of cytokines in activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. This minireview shows that HIF-1α in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of the T cell-mediated immune response and suggests potential new therapeutic strategies that target HIF-1α. (キーワード) Animals / Anoxia / Drug Discovery / Humans / Hypoxia-Inducible Factor 1, alpha Subunit / Immunity, Cellular / Reperfusion Injury / Tリンパ球 (T lymphocytes) / Vasculitis (出版サイトへのリンク) ● Publication site (DOI): 10.1254/jphs.10R22FM (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21422726 ● Summary page in Scopus @ Elsevier: 2-s2.0-79955046642 (DOI: 10.1254/jphs.10R22FM, PubMed: 21422726, Elsevier: Scopus)
48.	Keisuke Ishizawa, Masanori Yoshizumi, Yoshichika Kawai, Junji Terao, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Kazuo Minakuchi, Koichiro Tsuchiya and Toshiaki Tamaki : Pharmacology in health food: Metabolism of quercetin in vivo and its protective effect against arteriosclerosis, Journal of Pharmacological Sciences, Vol.115, No.4, 466-470, 2011. (要約) Quercetin, a member of the bioflavonoids family, has been proposed to have anti-atherogenic, anti-inflammatory, and anti-hypertensive properties leading to the beneficial effects against cardiovascular diseases. It was recently demonstrated that quercetin 3-O-β-D-glucuronide (Q3GA) is one of the major quercetin conjugates in human plasma, in which the aglycone could not be detected. Although most of the in vitro pharmacological studies have been carried out using only the quercetin aglycone form, experiments using Q3GA would be important to discover the preventive mechanisms of cardiovascular diseases by quercetin in vivo. Therefore we examined the effects of the chemically synthesized Q3GA, as an in vivo form, on vascular smooth muscle cell (VSMC) disorders related to the progression of arteriosclerosis. Platelet-derived growth factor-induced cell migration and proliferation were inhibited by Q3GA in VSMCs. Q3GA attenuated angiotensin II-induced VSMC hypertrophy via its inhibitory effect on JNK and the AP-1 signaling pathway. Q3GA scavenged 1,1-diphenyl-2-picrylhydrazyl radical measured by the electron paramagnetic resonance method. In addition, immunohistochemical studies with monoclonal antibody 14A2 targeting the Q3GA demonstrated that the positive staining specifically accumulates in human atherosclerotic lesions, but not in the normal aorta. These findings suggest Q3GA would be an active metabolite of quercetin in plasma and may have preventative effects on arteriosclerosis relevant to VSMC disorders. (キーワード) Animals / Antioxidants / Arteriosclerosis / Cell Movement / Cell Proliferation / Drug Evaluation, Preclinical / Free Radicals / Health Food / Humans / Hypertrophy / Muscle, Smooth, Vascular / Quercetin / Signal Transduction (出版サイトへのリンク) ● Publication site (DOI): 10.1254/jphs.10R38FM (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21436601 ● Search Scopus @ Elsevier (PMID): 21436601 ● Search Scopus @ Elsevier (DOI): 10.1254/jphs.10R38FM (DOI: 10.1254/jphs.10R38FM, PubMed: 21436601)
49.	Yuya Horinouchi, Koichiro Tsuchiya, Chiaki Taoka, Soichiro Tajima, Yoshitaka Kihira, Yuko Matsuda, Kozo Shishido, Masahiro Yoshida, Shuichi Hamano, Kazuyoshi Kawazoe, Yasumasa Ikeda, Keisuke Ishizawa, Shuhei Tomita and Toshiaki Tamaki : Antioxidant effects of photodegradation product of nifedipine, Chemical & Pharmaceutical Bulletin, Vol.59, No.2, 208-214, 2011. (要約) Recently, increasing evidence suggests that the antihypertensive drug nifedipine acts as a protective agent for endothelial cells, and that the activity is unrelated to its calcium channel blocking. Nifedipine is unstable under light and reportedly decomposes to a stable nitrosonifedipine (NO-NIF). NO-NIF has no antihypertensive effect, and it has been recognized as a contaminant of nifedipine. The present study for the first time demonstrated that NO-NIF changed to a NO-NIF radical in a time-dependent manner when it interacted with human umbilical vein endothelial cells (HUVECs). The electron paramagnetic resonance (EPR) signal of NO-NIF radicals in HUVECs showed an asymmetric pattern suggesting that the radicals were located in the membrane. The NO-NIF radicals had radical scavenging activity for 1,1-diphenyl-2-picrylhydrazyl, whereas neither NO-NIF nor nifedipine did. In addition, the NO-NIF radical more effectively quenched lipid peroxides than NO-NIF or nifedipine. Furthermore, NO-NIF attenuated the superoxide-derived free radicals in HUVECs stimulated with LY83583, and suppressed iron-nitrilotriacetic acid (Fe-NTA)-induced cytotoxicity in rat pheochromocytoma (PC12) cells. Our findings suggest that NO-NIF is a candidate for a new class of antioxidative drugs that protect cells against oxidative stress. (キーワード) Animals / Antioxidants / Cells, Cultured / Endothelial Cells / Humans / Nifedipine / PC12 Cells / Photolysis / Rats (出版サイトへのリンク) ● Publication site (DOI): 10.1248/cpb.59.208 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21297301 ● Summary page in Scopus @ Elsevier: 2-s2.0-79551489998 (DOI: 10.1248/cpb.59.208, PubMed: 21297301, Elsevier: Scopus)
50.	Takaaki Shimohata, Masayuki Nakano, Xin Lian, Tomomi Shigeyama, Hitomi Iba, Akiko Hamamoto, Masaki Yoshida, Nagakatsu Harada, Hironori Yamamoto, Masayuki Yamato, Kazuaki Mawatari, Toshiaki Tamaki, Yutaka Nakaya and Akira Takahashi : Vibrio parahaemolyticus infection induces modulation of IL-8 secretion through dual pathway via VP1680 in Caco-2 cells., The Journal of Infectious Diseases, Vol.203, No.4, 537-544, 2011. (要約) Vibrio parahaemolyticus causes acute gastroenteritis and inflammations in humans. A variety of pathogenic bacteria can stimulate mitogen-activated protein kinases (MAPKs) in host cells. Phosphorylation of MAPKs leads to production of interleukin (IL)- 8 and subsequently causes inflammations. Thus, MAPK cascades were strong candidates for the main signaling pathway of V. parahaemolyticus-induced acute inflammation. (キーワード) Caco-2 Cells / Humans / Interleukin-8 / Mitogen-Activated Protein Kinases / Phosphorylation / Signal Transduction / Vibrio parahaemolyticus / Viral Proteins / Virulence Factors (出版サイトへのリンク) ● Publication site (DOI): 10.1093/infdis/jiq070 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21177635 ● Search Scopus @ Elsevier (PMID): 21177635 ● Search Scopus @ Elsevier (DOI): 10.1093/infdis/jiq070 (DOI: 10.1093/infdis/jiq070, PubMed: 21177635)
51.	Yayoi Fukuhara, Koichiro Tsuchiya, Yuya Horinouchi, Soichiro Tajima, Yoshitaka Kihira, Shuichi Hamano, Kazuyoshi Kawazoe, Yasumasa Ikeda, Keisuke Ishizawa, Shuhei Tomita and Toshiaki Tamaki : Protective effect of photodegradation product of nifedipine against tumor necrosis factor alpha-induced oxidative stress in human glomerular endothelial cells, The Journal of Medical Investigation : JMI, Vol.58, No.1, 2, 118-126, 2011. (要約) Recently, increasing evidence suggests that the antihypertensive drug nifedipine acts as a protective agent for endothelial cells, and that the activity is unrelated to its calcium channel blocking. Nitrosonifedipine (NO-NIF) is metabolically and photochemically produced from nifedipine, and NO-NIF has been recognized as a contaminant of nifedipine because it has no antihypertensive effect. Treatment of tumor necrosis factor-α (TNF-α) suppressed the cell viability and facilitated the expression of Inter-Cellular Adhesion Molecule 1(ICAM-1) in human glomerular endothelial cells (HGECs) though, pretreatment of NO-NIF significantly recovered the TNF-α-induced cell damage to the same extent as Trolox-C did, and suppressed the ICAM-1 expression in a concentration dependent manner. In addition, NO-NIF inhibited the cell toxicity induced by cumene hydroperoxide, which hampers the integrity of cell membrane through oxidative stress, as effective as Trolox-c. These data suggest that NO-NIF is a candidate for a new class of antioxidative drug that protect cells against oxidative stress in glomerular endothelial cells. (キーワード) Antioxidants / Benzene Derivatives / Cell Survival / Cells, Cultured / Endothelial Cells / Humans / Intercellular Adhesion Molecule-1 / Kidney Glomerulus / Nifedipine / Nitroso Compounds / 酸化ストレス (oxidative stress) / Tumor Necrosis Factor-alpha (徳島大学機関リポジトリ) ● Metadata: 72667 (出版サイトへのリンク) ● Publication site (DOI): 10.2152/jmi.58.118 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21372496 ● CiNii @ 国立情報学研究所 (CRID): 1390001204242892288 ● Search Scopus @ Elsevier (PMID): 21372496 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.58.118 (徳島大学機関リポジトリ: 72667, DOI: 10.2152/jmi.58.118, PubMed: 21372496, CiNii: 1390001204242892288)
52.	Yasumasa Ikeda, Soichiro Tajima, Sumiko Yoshida, Noriko Yamano, Yoshitaka Kihira, Keisuke Ishizawa, Ken-ichi Aihara, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Deferoxamine promotes angiogenesis via the activation of vascular endothelial cell function., Atherosclerosis, Vol.215, No.2, 339-347, 2011. (要約) BACKGROUND: Deferoxamine (DFO), an iron chelator for disorders of excess iron, upregulates the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2), indicating that it affects angiogenesis. Herein, we clarify the effect and mechanism of action of DFO on angiogenesis. METHODS AND RESULTS: In an in vitro study, DFO increased endothelial nitric oxide synthesis (eNOS) phosphorylation in human aortic endothelial cells (HAECs), which were inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002. Tube formation, cell proliferation, and cell migration in HAECs were promoted by DFO, which were significantly reduced by LY294002. In an in vivo study, DFO promoted blood flow recovery in response to the hindlimb ischemia in mice with unilateral hindlimb surgery. The density of capillaries and arterioles in ischemic muscle was higher in DFO-treated mice compared to vehicle-treated mice. Endothelial cell proliferation increased and oxidative stress and apoptosis decreased in ischemic muscles of DFO-treated mice. The phosphorylation of Akt and eNOS on the ischemic side was elevated and urinary nitric oxide/nitric dioxide (NOx) excretion was higher in DFO-treated mice compared to vehicle-treated mice. The effect of DFO on angiogenesis was abolished in eNOS-deficient mice with hindlimb ischemia. CONCLUSION: These findings indicate that DFO promotes revascularization via the activation of vascular endothelial cell function by an Akt-eNOS-dependent mechanism. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.atherosclerosis.2011.01.009 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21315355 ● Search Scopus @ Elsevier (PMID): 21315355 ● Search Scopus @ Elsevier (DOI): 10.1016/j.atherosclerosis.2011.01.009 (DOI: 10.1016/j.atherosclerosis.2011.01.009, PubMed: 21315355)
53.	Yasumasa Ikeda, Ken-ichi Aihara, Masashi Akaike, Takashi Sato, Kazue Ishikawa, Takayuki Ise, Shusuke Yagi, Takashi Iwase, Yuka Ueda, Sumiko Yoshida, Hiroyuki Azuma, Kenneth Walsh, Toshiaki Tamaki, Shigeaki Kato and Toshio Matsumoto : Androgen receptor counteracts Doxorubicin-induced cardiotoxicity in male mice., Molecular Endocrinology, Vol.24, No.7, 1338-1348, 2010. (要約) Doxorubicin (Dox) has been used as a potent anticancer agent, but serious cardiotoxicity precludes its use in a wide range of patients. We have reported that the androgen-androgen receptor (AR) system plays important roles in cardiac growth and protection from angiotensin II-induced cardiac remodeling. The present study was undertaken to clarify whether the androgen-AR system exerts a cardioprotective effect against Dox-induced cardiotoxicity. Male AR knockout (ARKO) and age-matched littermate male wild-type (WT) mice at 25 wk of age were given ip injections of Dox (20 mg/kg) or a vehicle. The survival rate and left ventricular function in Dox-treated male ARKO mice were reduced compared with those in Dox-treated male WT mice. Electron microscopic study showed prominent vacuole formation of myocardial mitochondria in Dox-treated male ARKO mice. Cardiac oxidative stress and apoptosis of cardiomyocytes were increased more prominently by Dox treatment in male ARKO mice than in male WT mice. In addition, Dox-induced reduction in the expression of cardiac mitochondria transcription factor A (Tfam) and phosphorylation of serine-threonine kinase (Akt) was more pronounced in male ARKO mice than in male WT mice. In cardiac myoblast cells, testosterone up-regulated Akt phosphorylation and Tfam expression and exerted an antiapoptotic effect against Dox-induced cardiotoxicity. Collectively, the results demonstrate that Dox-induced cardiotoxicity is aggravated in male ARKO mice via exacerbation of mitochondrial damage and superoxide generation, leading to enhanced apoptosis of cardiomyocytes. Thus, the androgen-AR system is thought to counteract Dox-induced cardiotoxicity partly through activation of the Akt pathway and up-regulation of Tfam to protect cardiomyocytes from mitochondrial damage and apoptosis. (キーワード) Androgens / Animals / Antineoplastic Agents / Apoptosis / Blotting, Western / Cell Line / Cell Survival / DNA-Binding Proteins / Doxorubicin / Echocardiography / High Mobility Group Proteins / Immunoprecipitation / In Situ Nick-End Labeling / Male / Mice / Mice, Knockout / Microscopy, Electron / Myocardium / Myocytes, Cardiac / Oxidative Stress / Phosphorylation / Protein-Serine-Threonine Kinases / Rats / Receptors, Androgen / Superoxides / Testosterone / Thiobarbituric Acid Reactive Substances / Ventricular Function, Left (出版サイトへのリンク) ● Publication site (DOI): 10.1210/me.2009-0402 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20501642 ● Search Scopus @ Elsevier (PMID): 20501642 ● Search Scopus @ Elsevier (DOI): 10.1210/me.2009-0402 (DOI: 10.1210/me.2009-0402, PubMed: 20501642)
54.	Soichiro Tajima, Koichiro Tsuchiya, Yuya Horinouchi, Keisuke Ishizawa, Yasumasa Ikeda, Yoshitaka Kihira, Masayuki Shono, Kazuyoshi Kawazoe, Shuhei Tomita and Toshiaki Tamaki : Effect of angiotensin II on iron-transporting protein expression and subsequent intracellular labile iron concentration in human glomerular endothelial cells, Hypertension Research, Vol.33, No.7, 713-721, 2010. (要約) Angiotensin II (Ang II)-induced endothelial injury, which is associated with atherosclerosis, is believed to be mediated by intracellular reactive oxygen species (ROS) through stimulation of nicotinamide adenine dinucleotide phosphate oxidase (NOX). Iron is essential for the amplification of oxidative stress. In this study, we investigated whether Ang II altered iron metabolism and whether the Ang II-induced endothelial injury is attributable to changes in iron metabolism of human glomerular endothelial cells (HGECs). When 90% iron-saturated human transferrin (90% Tf) was applied to HGECs without Ang II, the labile ferrous iron level was same as the effect of control in spite of a significant increase in the total cellular iron concentration. Treatment with Ang II and 30% Tf or 90% Tf significantly (P<0.01) increased the intracellular iron concentration, as well as labile ferrous iron and protein oxidation levels, compared with the effect of separate administration of each compound. Ang II treatment facilitated the protein expression of the Tf receptor, divalent metal transporter 1, and ferroportin 1 in a dose- and time-dependent manner. It was also found that simultaneous exposure of HGECs to Ang II and 90% Tf accelerated hydroxyl radical production, as shown by using an electron paramagnetic resonance spectrometer. These results suggest that Ang II not only induces production of ROS by NOX activation but also iron incorporation followed by an increase in labile iron in HGECs. Both of these events may participate in the progression of oxidative stress because of endothelial cell dysfunction through ferrous iron-mediated ROS generation. (キーワード) Angiotensin II / Cation Transport Proteins / Endothelial Cells / Humans / Hydroxyl Radical / Iron / Kidney Glomerulus / 酸化と還元 (oxidation and reduction) / Receptors, Transferrin / Transferrin (出版サイトへのリンク) ● Publication site (DOI): 10.1038/hr.2010.63 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20431588 ● Summary page in Scopus @ Elsevier: 2-s2.0-77954369377 (DOI: 10.1038/hr.2010.63, PubMed: 20431588, Elsevier: Scopus)
55.	Keisuke Ishizawa, Yuki Izawa-Ishizawa, Narantungalag Dorjsuren, Erika Miki, Yoshitaka Kihira, Yasumasa Ikeda, Shuichi Hamano, Kazuyoshi Kawazoe, Kazuo Minakuchi, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Angiotensin II receptor blocker attenuates PDGF-induced mesangial cell migration in a receptor-independent manner, Nephrology, Dialysis, Transplantation, Vol.25, No.2, 364-372, 2010. (要約) Clinical studies have shown that angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) are able to provide renoprotection independent of their blood pressure lowering effects. ARBs also are reported to suppress oxidative stress, inflammation and certain other cellular responses in a receptor-independent manner. We investigated the effects of an ARB, olmesartan, on the cell migration induced by platelet-derived growth factor (PDGF), a major mitogen involved in the pathogenesis of glomerulonephritis in rat mesangial cells (RMCs). Cell migration was determined by a modified Boyden chamber assay. The intracellular signalling pathway was examined by western blotting. AT1 receptor expression was knocked down by small interfering RNAs. The intracellular reactive oxygen species (ROS) was measured by using a fluorescent probe. The O(2)(.-) scavenging activities were studied by the electron paramagnetic resonance-spin trapping method. PDGF-induced cell migration was inhibited by olmesartan in AT1 receptor knockdown RMCs. Olmesartan attenuated big mitogen-activated protein (MAP) kinase 1 (BMK1) and Src activation by PDGF in AT1 receptor knockdown RMCs. PDGF-induced BMK1 activation was suppressed by the Src family tyrosine kinase inhibitors, indicating that Src exists upstream of BMK1. The NADPH oxidase inhibitors inhibited not only PDGF-induced BMK1 and Src activation but also RMC migration. The elevation in ROS generation induced by PDGF was decreased by olmesartan. Olmesartan displayed neither directly ROS scavenging activity nor the inhibition of ROS-mediated intracellular signalling in RMCs. Olmesartan attenuates ROS generation by PDGF, leading to the subsequent inhibition of Src/ BMK1/migration in an AT1 receptor-independent manner in RMCs. (キーワード) Angiotensin II Type 1 Receptor Blockers / Animals / Cell Movement / Cells, Cultured / Imidazoles / Male / Mesangial Cells / Platelet-Derived Growth Factor / Rats / Rats, Sprague-Dawley / Signal Transduction / Tetrazoles (出版サイトへのリンク) ● Publication site (DOI): 10.1093/ndt/gfp520 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19812233 ● Search Scopus @ Elsevier (PMID): 19812233 ● Search Scopus @ Elsevier (DOI): 10.1093/ndt/gfp520 (DOI: 10.1093/ndt/gfp520, PubMed: 19812233)
56.	Koichiro Tsuchiya, Shuhei Tomita, Keisuke Ishizawa, Shinji Abe, Yasumasa Ikeda, Yoshitaka Kihira and Toshiaki Tamaki : Dietary nitrite ameliorates renal injury in l-NAME-induced hypertensive rats, Nitric Oxide: Biology and Chemistry, Vol.22, No.2, 98-103, 2010. (要約) Nitric oxide (NO) has numerous important functions in the kidney, and long-term blockage of nitric oxide synthases in rats by L-NAME results in severe hypertension and progressive kidney damage. On the other hand, NO production seems to be low in patients with chronic kidney disease (CKD), and NO deficiency may play a role in CKD progression. In this review, we summarized the mechanisms of amelioration of renal injury induced by L-NAME treated rats by treatment of nitrite. First, we demonstrate whether orally-administrated nitrite-derived NO can shift to the circulation. When 3mg/kg body weight Na(15)NO(2) was orally administered to rats, an apparent EPR signal derived from Hb(15)NO (A(z)=23.4 gauss) appeared in the blood, indicating that orally ingested nitrite can be a source of NO in vivo. Next, in order to clarify the capacity of nitrite to prevent renal disease, we administered low-dose nitrite (LDN: 0.1mg of sodium nitrite in 1L of drinking water), medium-dose nitrite (MDN: 1mg sodium nitrite/L, which corresponds to the amount of nitrite ingested by vegetarians), or high-dose nitrite (HDN: 10mg sodium nitrite/L) to rats simultaneously with L-NAME (1 g l-NAME/L) for 8 weeks, then examined the blood NO level as a hemoglobin-NO adduct (iron-nitrosyl-hemoglobin) using electron paramagnetic resonance spectroscopy, urinary protein excretion, and renal histological changes at the end of the experiment. It was found that oral administration of MDN and HDN but not LDN increased the blood iron-nitrosyl-hemoglobin concentration to the normal level, ameliorated the L-NAME-induced proteinuria, and reduced renal histological damage. The findings demonstrate that chronic administration of a mid-level dietary dose of nitrite restores the circulating iron-nitrosyl-hemoglobin levels reduced by L-NAME and that maintenance of the circulating iron-nitrosyl-hemoglobin level in a controlled range protects against L-NAME-induced renal injury. Taking these findings together, we propose that dietary supplementation of nitrite is a potentially useful nonpharmacological strategy for maintaining circulating NO level in order to prevent or slow the progression of renal disease. It had been believed that nitrite could result in intragastric formation of nitrosamines, which had been linked to esophageal and other gastrointestinal cancers. However, there is no positive association between the intake of nitrate or nitrite and gastric and pancreatic cancer by recent researches. Furthermore, nitrate-derived NO formation pathway is a possible mechanism for the hypotensive effect of vegetable- and fruit-rich diets, which may explain, at least in part, the mechanism of the Dietary Approach to Stop Hypertension (DASH) diet-induced hypotensive and organ-protective effects. Further research is needed to investigate the interaction between nitrite-nitrate intakes and human health. (キーワード) Animals / Diet / Hypertension / Kidney Diseases / NG-Nitroarginine Methyl Ester / Rats / Sodium Nitrite (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.niox.2009.12.002 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20005970 ● Search Scopus @ Elsevier (PMID): 20005970 ● Search Scopus @ Elsevier (DOI): 10.1016/j.niox.2009.12.002 (DOI: 10.1016/j.niox.2009.12.002, PubMed: 20005970)
57.	Hirotsugu Kurobe, Masahisa Urata, Masaki Ueno, Masaaki Ueki, Shiro Ono, Yuki Izawa-Ishizawa, Yayoi Fukuhara, Yu Lei, Adiratna Mat Ripen, Tamotsu Kanbara, Ken-ichi Aihara, Keisuke Ishizawa, Masashi Akaike, Frank J. Gonzalez, Toshiaki Tamaki, Yousuke Takahama, Masanori Yoshizumi, Tetsuya Kitagawa and Shuhei Tomita : Role of Hypoxia-Inducible Factor 1α in T Cells as a Negative Regulator in Development of Vascular Remodeling, Arteriosclerosis, Thrombosis, and Vascular Biology, Vol.30, No.2, 210-217, 2010. (要約) Recent studies have shown that the cellular immune response in the development of vascular remodeling modulates the resulting pathological alterations. We show that hypoxia-inducible factor 1 (Hif-1) (specifically expressed in T cells) is involved in the immune response to vascular remodeling that accompanies arteriosclerosis. To study the role of T cells in the development of vascular remodeling, femoral arterial injury induced by an external vascular polyethylene cuff was examined in mice lacking Hif-1 (specifically in T cells). We found that cuff placement caused prominent neointimal hyperplasia of the femoral artery in Hif-1- (T-cell)-deficient mice compared with that in control mice and that infiltration of inflammatory cells at the adventitia was markedly increased in the mutant mice. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice showed enhanced production of cytokines by activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. The results of this study revealed that Hif-1alpha in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of T cell-mediated immune response. Potential new therapeutic strategies that target Hif-1alpha are described. (キーワード) Animals / Antibody Formation / Arteriosclerosis / Cell Hypoxia / Cell Proliferation / Chemokine CXCL12 / Chemotaxis, Leukocyte / 細胞質分裂 (cytokinesis) / Disease Models, Animal / Femoral Artery / Hyperplasia / Hypoxia-Inducible Factor 1, alpha Subunit / Immunity, Cellular / 免疫組織化学 (immunohistochemistry) / Lymphocyte Activation / 男性 (male) / Mice / ノックアウトマウス (knockout mice) / Nitroimidazoles / Receptors, Antigen, T-Cell / Tリンパ球 (T lymphocytes) / Thymus Gland / Time Factors / Tunica Intima (出版サイトへのリンク) ● Publication site (DOI): 10.1161/ATVBAHA.109.192666 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20007912 ● Search Scopus @ Elsevier (PMID): 20007912 ● Search Scopus @ Elsevier (DOI): 10.1161/ATVBAHA.109.192666 (DOI: 10.1161/ATVBAHA.109.192666, PubMed: 20007912)
58.	Maki Urushihara, Masanori Takamatsu, Maki Shimizu, Shuji Kondo, Yukiko Kinoshita, Kenichi Suga, Akiko Kitamura, Sato Matsuura, Masanori Yoshizumi, Toshiaki Tamaki, Hiroshi Kawachi and Shoji Kagami : ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis., American Journal of Physiology, Renal Physiology, Vol.298, No.1, F167-76, 2010. (要約) The mitogen-activated protein kinase (MAPK) cascade plays an important role in the regulation of various cellular functions in glomerulonephritis (GN). Here, we investigated whether extracellular signal-regulated kinase 5 (ERK5), a member of the MAPK family, is involved in the pathogenesis of chronic mesangioproliferative GN, using a rat model induced by uninephrectomy and anti-Thy-1 antibody injection. Immunostaining of kidneys obtained at different time points revealed that phospho-ERK5 was weakly expressed in control glomeruli but dramatically increased in a typical mesangial pattern after 28 and 56 days of GN. A semiquantitative assessment indicated that glomerular phospho-ERK5 expression closely paralleled the accumulation of extracellular matrix (ECM), collagen type I, as well as glomerular expression of reactive oxygen species (ROS) and ANG II. On the other hand, phospho-ERK1/2 expression increased on day 7 during the phase of enhanced mesangial cell (MC) proliferation and decreased thereafter. H(2)O(2) and ANG II each induced ERK5 phosphorylation by cultured rat MCs. Costimulation with both H(2)O(2) and ANG II synergistically increased ERK5 phosphorylation in MCs. Cultured MCs transfected with ERK5-specific small interference RNA showed a significant decrease in H(2)O(2) or ANG II-induced cell viability and soluble collagen secretion compared with control cells. Treatment of GN rats with an ANG II type 1 receptor blocker resulted in significant decreases in phospho-ERK5 expression and collagen accumulation accompanied by remarkable histological improvement. Taken together, these results suggest that MC ERK5 phosphorylation by ANG II or H(2)O(2) enhances cell viability and ECM accumulation in an experimental model of chronic GN. (キーワード) Angiotensin II / Animals / Cell Survival / Cells, Cultured / Collagen / Disease Models, Animal / Disease Progression / Extracellular Matrix / Glomerulonephritis / Hydrogen Peroxide / Mesangial Cells / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinase 7 / Phosphorylation / Rats / Rats, Inbred Strains (出版サイトへのリンク) ● Publication site (DOI): 10.1152/ajprenal.00124.2009 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19846573 ● Search Scopus @ Elsevier (PMID): 19846573 ● Search Scopus @ Elsevier (DOI): 10.1152/ajprenal.00124.2009 (DOI: 10.1152/ajprenal.00124.2009, PubMed: 19846573)
59.	Keisuke Ishizawa, Narantungalag Dorjsuren, Yuki Izawa-Ishizawa, Rika Sugimoto, Yasumasa Ikeda, Yoshitaka Kihira, Kazuyoshi Kawazoe, Shuhei Tomita, Koichiro Tsuchiya, Kazuo Minakuchi and Toshiaki Tamaki : Inhibitory effects of adiponectin on platelet-derived growth factor-induced mesangial cell migration, The Journal of Endocrinology, Vol.202, No.2, 309-316, 2009. (要約) Adiponectin, an adipocyte-derived hormone, has been involved in metabolic syndrome, a known risk factor for the development of chronic kidney disease (CKD). Recent studies have demonstrated that plasma adiponectin levels are elevated when kidney function declines in patients with CKD. Excessive mesangial cell (MC) turnover is one of the important features of CKD. The aim of the present study is to elucidate the effects of adiponectin on platelet-derived growth factor (PDGF)-induced cell migration and intracellular signaling pathways, in cultured rat MCs (RMCs). PDGF-induced RMC migration was significantly inhibited by the pretreatment of adiponectin. Adiponectin alone had no effect on RMC migration. Big mitogen-activated protein (MAP) kinase 1 (BMK1), p38 MAP kinase, and Akt were activated by PDGF stimulation in a time- and concentration-dependent manner in RMC. Adiponectin alone did not affect BMK1, p38 MAP kinase, and Akt phosphorylations in RMC. PDGF-induced BMK1 and p38 MAP kinase phosphorylations were significantly attenuated by the pretreatment of adiponectin in RMCs. On the other hand, the phosphorylation of Akt by PDGF was not diminished by the pretreatment of adiponectin. Adiponectin had no effects on PDGF-receptor autophosphorylation by PDGF. We also confirmed that PDGF-induced RMC migration was significantly suppressed by siBMK1 transfection or SB203580, a p38 MAP kinase inhibitor. From these findings, it is implied that the elevated plasma adiponectin levels in patients with CKD might play a compensatory role aimed at counteracting renal dysfunction related to MC disorders. (キーワード) Adiponectin / Animals / Cell Movement / Cells, Cultured / Dose-Response Relationship, Drug / Enzyme Inhibitors / Glomerular Mesangium / Imidazoles / Male / Mitogen-Activated Protein Kinase 7 / Phosphorylation / Platelet-Derived Growth Factor / Pyridines / RNA, Small Interfering / Rats / Rats, Sprague-Dawley / Recombinant Proteins / p38 Mitogen-Activated Protein Kinases (出版サイトへのリンク) ● Publication site (DOI): 10.1677/JOE-08-0469 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19460854 ● Search Scopus @ Elsevier (PMID): 19460854 ● Search Scopus @ Elsevier (DOI): 10.1677/JOE-08-0469 (DOI: 10.1677/JOE-08-0469, PubMed: 19460854)
60.	Yuki Motobayashi, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Sakiko Orino, Kunihisa Yamaguchi, Kazuyoshi Kawazoe, Shuichi Hamano, Koichiro Tsuchiya, Shuhei Tomita and Toshiaki Tamaki : Adiponectin inhibits insulin-like growth factor-1-induced cell migration by the suppression of extracellular signal-regulated kinase 1/2 activation, but not Akt in vascular smooth muscle cells, Hypertension Research, Vol.32, No.3, 188-193, 2009. (要約) Adiponectin, an adipocyte-derived hormone, has been proposed to show antiatherogenic properties through the inhibitory effects against various growth factors. Insulin-like growth factor-1 (IGF-1) is one of the potent mitogens, which has been considered to play important roles in both atherogenesis and plaque stabilization in accordance to the phase of atherosclerosis. The aim of this study is to elucidate the adiponectin effects on IGF-1-induced cell migration and its intracellular signaling pathways in vascular smooth muscle cells (VSMCs). In this study, we assessed cell migration and several kinase activities in cultured rat aortic smooth muscle cells (RASMCs). Adiponectin pretreatment suppressed IGF-1-induced cell migration and extracellular signal-regulated kinase (ERK)1/2 activation, which is one of the major mediators for IGF-1-induced cell migration. In RASMCs, adiponectin and 5-aminoimidazole-4-carboxamide riboside (AICAR), a 5'-AMP-activated protein kinase (AMPK) activator, stimulated AMPK activation. AMPK activation by AICAR inhibited IGF-1-induced ERK1/2 activation and cell migration in RASMCs. On the other hand, phosphorylation of Akt and Bad, proapoptotic molecules of the Bcl-2 family, which were increased by IGF-1 stimulation, was not diminished by the pretreatment with adiponectin. It was shown that adiponectin inhibited IGF-1-induced VSMC migration through suppression of ERK1/2 activation, which might be implicated in AMPK activation. Furthermore, adiponectin selectively inhibited ERK1/2 pathway, not Akt-Bad pathway, stimulated by IGF-1. From these findings, it was implied that adiponectin suppressed IGF-1-induced VSMC migration and its signaling selectivity. (キーワード) Adiponectin / Aminoimidazole Carboxamide / Animals / Blotting, Western / Cell Movement / Enzyme Activation / Enzyme Activators / Insulin-Like Growth Factor I / Male / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Myocytes, Smooth Muscle / Oncogene Protein v-akt / Phosphorylation / Rats / Rats, Sprague-Dawley / Ribonucleotides / シグナル伝達 (signal transduction) / bcl-Associated Death Protein / p38 Mitogen-Activated Protein Kinases (出版サイトへのリンク) ● Publication site (DOI): 10.1038/hr.2008.19 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19262481 ● Search Scopus @ Elsevier (PMID): 19262481 ● Search Scopus @ Elsevier (DOI): 10.1038/hr.2008.19 (DOI: 10.1038/hr.2008.19, PubMed: 19262481)
61.	Keisuke Ishizawa, Yuki Izawa-Ishizawa, Sachiyo Ohnishi, Yuki Motobayashi, Kazuyoshi Kawazoe, Shuichi Hamano, Koichiro Tsuchiya, Shuhei Tomita, Kazuo Minakuchi and Toshiaki Tamaki : Quercetin Glucuronide Inhibits Cell Migration and Proliferation by Platelet-Derived Growth Factor in Vascular Smooth Muscle Cells, Journal of Pharmacological Sciences, Vol.109, No.2, 257-264, 2009. (要約) Many epidemiologic studies have reported that dietary flavonoids provide protection against cardiovascular disease. Quercetin, a member of the bioflavonoids family, has been proposed to have anti-inflammatory, anti-atherogenic, and anti-hypertensive properties leading to the beneficial effects against cardiovascular diseases. Recent studies demonstrated that orally administered quercetin appeared in plasma as glucuronide-conjugated forms in rats and humans. Therefore, we examined the effect of chemically synthesized quercetin glucuronide on platelet-derived growth factor (PDGF)-induced cell migration and kinase activation in cultured rat aortic smooth muscle cells (RASMCs). PDGF-induced RASMC migration was inhibited by quercetin 3-O-beta-D-glucuronide (Q3GA). Q3GA also attenuated PDGF-induced cell proliferation in RASMCs. PDGF activated extracellular-signal regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (MAP) kinase, and Akt in RASMCs. PDGF-induced JNK and Akt activations were suppressed by Q3GA, whereas ERK1/2 and p38 MAP kinase activations were not affected. We also confirmed that PDGF-induced JNK and Akt activations were inhibited by antioxidants, N-acetylcysteine and diphenyleneiodonium chloride, in RASMCs. These findings suggest Q3GA would be an active metabolite of quercetin in plasma and may possess preventing effects for cardiovascular diseases relevant to vascular smooth muscle cell disorders. (キーワード) Animals / Antioxidants / Cell Movement / Cell Proliferation / Cells, Cultured / Glucuronides / MAP Kinase Kinase 4 / Male / Muscle, Smooth, Vascular / Platelet-Derived Growth Factor / Quercetin / Rats / Rats, Sprague-Dawley (出版サイトへのリンク) ● Publication site (DOI): 10.1254/jphs.08236FP (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19202317 ● Search Scopus @ Elsevier (PMID): 19202317 ● Search Scopus @ Elsevier (DOI): 10.1254/jphs.08236FP (DOI: 10.1254/jphs.08236FP, PubMed: 19202317)
62.	Keisuke Ishizawa, Kunihisa Yamaguchi, Yuya Horinouchi, Yayoi Fukuhara, Soichiro Tajima, Shuichi Hamano, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Toward drug discovery for overcoming CKD: Development of drugs on endothelial cell protection for overcoming CKD, Journal of Pharmacological Sciences, Vol.109, No.1, 14-19, 2009. (要約) Chronic kidney disease (CKD) is becoming a major public health problem worldwide. It is important to protect endothelial function in CKD treatment because injury of the endothelium is a critical event for the generation and progression of CKD. Recently, clinical studies showed that nifedipine, an antihypertensive drug, acts as a protective agent of endothelial cells (ECs). Nifedipine is reported to partially decompose to a nitrosonifedipine that has high reactivity against lipid-derived radicals in vitro. However, it is still unclear whether nitrosonifedipine is a biologically active agent against endothelial injury. We observed that nitrosonifedipine was converted to radical form by reaction with cultured ECs. The cumene hydroperoxide mediated cytotoxity was reduced by nitrosonifedipine in cultured human glomerular ECs (HGECs). Also nitrosonifedipine suppressed the expression of TNF-alpha-induced intercellular cell adhesion molecule-1 in HGECs. Chronic administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) caused systemic arterial hypertension, endothelial injury, and renal dysfunction. In L-NAME-induced hypertensive rats, nitrosonifedipine treatment improved not only the acetylcholine-induced vasodilation of the aortic rings, but also renal dysfunction such as increasing the levels of serum creatinine and urinary protein excretion. Our preliminary data suggest that nitrosonifedipine is a new and useful drug for the treatment of CKD involving ameliorating effects on EC disorder. (キーワード) Animals / Cells, Cultured / Drug Discovery / Endothelial Cells / Humans / Kidney Failure, Chronic / Molecular Structure / Nifedipine / Nitroso Compounds / Vasodilator Agents (出版サイトへのリンク) ● Publication site (DOI): 10.1254/jphs.08R08FM (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19151535 ● Search Scopus @ Elsevier (PMID): 19151535 ● Search Scopus @ Elsevier (DOI): 10.1254/jphs.08R08FM (DOI: 10.1254/jphs.08R08FM, PubMed: 19151535)
63.	Hideki Ohnishi, Satoshi Iwanaga, Kazuyoshi Kawazoe, Keisuke Ishizawa, Sakiko Orino, Shuhei Tomita, Koichiro Tsuchiya, Yasuhisa Kanematsu, Nagakatsu Harada, Kazuhiro Mori, Tomoko Tsuchihashi, Yasuko Ishikawa and Toshiaki Tamaki : Effect of iron-quercetin complex on reduction of nitrite in in vitro and in vivo systems, Journal of Agricultural and Food Chemistry, Vol.56, No.21, 10092-10098, 2008. (要約) This study investigated whether reducing agents such as quercetin and iron(II) facilitate formation of nitric oxide (NO) gas from orally ingested nitrite in an vivo study. When 3 mg/kg Na (15)NO2 was orally administered to rats with or without iron(II) or quercetin, Hb (15)NO, which is indicative of systemic (15)NO, was detected in the blood, with the maximum blood concentration of Hb (15)NO at 15 min after nitrite or nitrite plus quercetin treatment, whereas after administration of nitrite plus iron(II) or nitrite plus iron(II) and quercetin, the time was shortened to 10 min. Interestingly, iron(II), quercetin, or iron(II) plus quercetin did not affect the total amount of Hb (15)NO generated from orally administered Na (15)NO2. However, the systemic nitrite concentration was significantly decreased in the presence of iron(II) or iron(II) plus quercetin. These results may indicate that iron(II) is critical to the generation of NO gas from nitrite, whereas quercetin contributed little under the in vivo experimental conditions. (キーワード) Animals / Antioxidants / Iron / Male / Nitrates / Nitric Oxide / Nitrites / Oxidation-Reduction / Quercetin / Rats / Rats, Sprague-Dawley (出版サイトへのリンク) ● Publication site (DOI): 10.1021/jf801010j (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18831560 ● Search Scopus @ Elsevier (PMID): 18831560 ● Search Scopus @ Elsevier (DOI): 10.1021/jf801010j (DOI: 10.1021/jf801010j, PubMed: 18831560)
64.	Yasuhisa Kanematsu, Kunihisa Yamaguchi, Hideki Ohnishi, Yuki Motobayashi, Keisuke Ishizawa, Yuki Izawa, Kazuyoshi Kawazoe, Shuji Kondo, Shoji Kagami, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury in L-NAME-induced hypertensive rats, American Journal of Physiology, Renal Physiology, Vol.295, No.5, F1457-F1462, 2008. (要約) We have reported that pharmacological doses of oral nitrite increase circulating nitric oxide (NO) and exert hypotensive effects in Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. In this study, we examined the effect of a chronic dietary dose of nitrite on the hypertension and renal damage induced by chronic L-NAME administration in rats. The animals were administered tap water containing L-NAME (1 g/l) or L-NAME + nitrite (low dose: 0.1 mg/l, medium dose: 1 mg/l, high dose: 10 mg/l) for 8 wk. We evaluated blood NO levels as hemoglobin-NO adducts (iron-nitrosyl-hemoglobin), using an electron paramagnetic resonance method. Chronic administration of L-NAME for 8 wk induced hypertension and renal injury and reduced the blood iron-nitrosyl-hemoglobin level (control 38.8 +/- 8.9 vs. L-NAME 6.0 +/- 3.1 arbitrary units). Coadministration of a low dose of nitrite with L-NAME did not change the reduced iron-nitrosyl-hemoglobin signal and did not improve the L-NAME-induced renal injury. The blood iron-nitrosyl-hemoglobin signals of the medium dose and high dose of nitrite were significantly higher than that of L-NAME alone. Chronic administration of a medium dose of nitrite attenuated L-NAME-induced renal histological changes and proteinuria. A high dose of nitrite also attenuated L-NAME-induced renal injury. These findings suggest that dietary doses of nitrite that protect the kidney are associated with significant increase in iron-nitrosyl-hemoglobin levels. We conclude that dietary nitrite-derived NO generation may serve as a backup system when the nitric oxide synthase/L-arginine-dependent NO generation system is compromised. (キーワード) Administration, Oral / Animals / 血圧 (blood pressure) / Body Weight / Diet / Hemoglobin A, Glycosylated / Hypertension / Kidney / Kidney Diseases / Kidney Glomerulus / Male / NG-Nitroarginine Methyl Ester / Nitrates / 一酸化窒素 (nitric oxide) / Proteinuria / Rats / Rats, Sprague-Dawley (出版サイトへのリンク) ● Publication site (DOI): 10.1152/ajprenal.00621.2007 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18753302 ● Search Scopus @ Elsevier (PMID): 18753302 ● Search Scopus @ Elsevier (DOI): 10.1152/ajprenal.00621.2007 (DOI: 10.1152/ajprenal.00621.2007, PubMed: 18753302)
65.	Masahiro Watanabe, Takenori Yamamoto, Rei Kakuhata, Naoto Okada, Kazuaki Kajimoto, Naoshi Yamazaki, Masatoshi Kataoka, Yoshinobu Baba, Toshiaki Tamaki and Yasuo Shinohara : Synchronized changes in transcript levels of genes activating cold exposure-induced thermogenesis in brown adipose tissue of experimental animals., Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol.1777, No.1, 104-112, 2008. (要約) To identify genes whose expression in brown adipose tissue (BAT) is up- or down-regulated in cold-exposed rats, we performed microarray analysis of RNA samples prepared from the BAT of cold-exposed rats and of rats kept at room temperature. Previously reported elevations of transcript levels of uncoupling protein (UCP1), type II iodothyronine deiodinase (DIO2), and type III adenylate cyclase (AC3) in the BAT of cold-exposed rats over those in that of rats maintained at room temperature were confirmed. In addition to these changes, remarkable elevations of the transcript levels of several genes that seemed to be associated with the processes of cell-cycle regulation and DNA replication were detected in the BAT of cold-exposed rats, possibly reflecting the significant proliferation of brown adipocytes in response to cold exposure. Up-regulation of the gene encoding sarcomeric mitochondrial type creatine kinase in the BAT of cold-exposed rats was also detected by microarray analysis, but subsequent Northern analysis revealed that the expression of not only the sarcomeric mitochondrial type enzyme, but also that of 2 other subtypes, i.e., cytoplasmic brain type and cytoplasmic muscle type, was elevated in the BAT of cold-exposed rats. Microarray analysis also revealed a significant expression of myoglobin in BAT and its elevation in the BAT of cold-exposed rats, and this result was supported by calibrated Northern analysis. On the contrary, several genes such as regulator of G-protein signaling 2 and IMP dehydrogenase 1 were down-regulated in the BAT of cold-exposed rats. The physiological meaning of these changes accompanying cold exposure was discussed. (キーワード) Adenylate Cyclase / Adipose Tissue, Brown / Amino Acid Sequence / Animals / Cold Temperature / Creatine Kinase / Gene Expression Regulation / Iodide Peroxidase / Ion Channels / Male / Mitochondrial Proteins / Molecular Sequence Data / Oligonucleotide Array Sequence Analysis / RNA, Messenger / Rats / Rats, Wistar / Thermogenesis / Voltage-Dependent Anion Channel 1 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.bbabio.2007.10.014 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18036333 ● Search Scopus @ Elsevier (PMID): 18036333 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbabio.2007.10.014 (DOI: 10.1016/j.bbabio.2007.10.014, PubMed: 18036333)
66.	Yuki Izawa, Masanori Yoshizumi, Keisuke Ishizawa, Yoshiko Fujita, Shuji Kondo, Shoji Kagami, Kazuyoshi Kawazoe, Koichiro Tsuchiya, Shuhei Tomita and Toshiaki Tamaki : Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration, Hypertension Research, Vol.30, No.11, 1107-1117, 2007. (要約) Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling. (キーワード) Animals / Cell Movement / Humans / MAP Kinase Kinase 5 / Male / Mice / Mice, Inbred C57BL / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinase 7 / Muscle, Smooth, Vascular / Myocytes, Smooth Muscle / Phosphoproteins / Phosphorylation / Platelet-Derived Growth Factor / Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Rats (出版サイトへのリンク) ● Publication site (DOI): 10.1291/hypres.30.1107 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18250560 ● Search Scopus @ Elsevier (PMID): 18250560 ● Search Scopus @ Elsevier (DOI): 10.1291/hypres.30.1107 (DOI: 10.1291/hypres.30.1107, PubMed: 18250560)
67.	Ali Nermin, Masanori Yoshizumi, Seiji Yano, Saburo Sone, Hideki Ohnishi, Keisuke Ishizawa, Yasuhisa Kanematsu, Koichiro Tsuchiya and Toshiaki Tamaki : The novel Src kinase inhibitor M475271 inhibits VEGF-induced vascular endothelial-cadherin and β-catenin phosphorylation but increases their association, Journal of Pharmacological Sciences, Vol.102, No.1, 112-120, 2006. (要約) M475271, 4-quinazolinamine, N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl) methoxy]-(9Cl), is a new anilinoquinazoline derivative that displays selective inhibition of Src kinase activity and tumor growth in vivo. Vascular endothelial growth factor (VEGF)-induced angiogenesis plays a pivotal role in tumor growth and metastasis. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule that can interact with the cytoskeleton via several anchoring molecules such as beta-catenin. Here, we examined the effect of M475271 on VE-cadherin and beta-catenin phosphorylation and association. We also examined its effect on VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation. The findings reveal pretreatment with M475271 significantly inhibits VEGF-induced VE-cadherin and beta-catenin phosphorylation. However, M475271 significantly increases VE-cadherin and beta-catenin association compared to the VEGF-treated group. Confocal laser microscopic examination confirmed the augmentation effect of M475271 on VE-cadherin and beta-catenin association. Finally, M475271 was shown to have inhibitory effects comparable to those of PP2 and Herbimycin A on VEGF-induced HUVEC proliferation, migration, and tube formation. These findings suggest that M475271 attenuates VEGF-induced angiogenesis by maintaining cell-cell junction stability. Although the involvement of other signaling molecules cannot be ruled out, M475271 has potential as a drug for the inhibition of the angiogenesis needed for tumor growth and metastasis. (キーワード) M475271 / vascular endothelial growth factor (出版サイトへのリンク) ● Publication site (DOI): 10.1254/jphs.FP0060357 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16974068 ● Search Scopus @ Elsevier (PMID): 16974068 ● Search Scopus @ Elsevier (DOI): 10.1254/jphs.FP0060357 (DOI: 10.1254/jphs.FP0060357, PubMed: 16974068)
68.	Shinji Abe, Hideki Ohnishi, Koichiro Tsuchiya, Keisuke Ishizawa, Mayumi Torii, Yasuhisa Kanematsu, Kazuyoshi Kawazoe, Kazuo Minakuchi, Masanori Yoshizumi and Toshiaki Tamaki : Calcium and reactive oxygen species mediated Zn²⁺-induced apoptosis in PC12 cells, Journal of Pharmacological Sciences, Vol.102, No.1, 103-111, 2006. (要約) The release of excessive Zn(2+) from presynaptic boutons into extracellular regions contributes to neuronal apoptotic events, which result in neuronal cell death. However, the mechanisms of Zn(2+)-induced neuronal cell death are still unclear. Therefore, we investigated the dynamics of intracellular Zn(2+), calcium, and reactive oxygen species in PC12 cells. The addition of Zn(2+) produced cell death in a concentration- and time-dependent manner. (45)Ca(2+) influx occurred just after the treatment with Zn(2+), although subsequent hydroxyl radical (()OH) production did not begin until 3 h after Zn(2+) exposure. ()OH production was significantly attenuated in Ca(2+)-free medium or by L-type Ca(2+) channel antagonist treatment, but it was independent of the intracellular Zn(2+) content. Dantrolene treatment had no protective effects against Zn(2+)-induced cell death. Treatment with N-acetyl-L-cysteine blocked ()OH generation and subsequent cell death. These data indicate that Ca(2+) influx and subsequent ()OH production are critical events in Zn(2+)-induced toxicity in PC12 cells. (キーワード) Acetylcysteine / Animals / Apoptosis / Bisbenzimidazole / Calcium / Calcium Channel Blockers / Calcium Channels, L-Type / Calcium Radioisotopes / Cell Survival / Dantrolene / Fluorescent Dyes / Free Radical Scavengers / Hydroxyl Radical / PC12 Cells / Rats / Reactive Oxygen Species / Spectrophotometry, Atomic / Zinc (出版サイトへのリンク) ● Publication site (DOI): 10.1254/jphs.FP0060342 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16990703 ● Search Scopus @ Elsevier (PMID): 16990703 ● Search Scopus @ Elsevier (DOI): 10.1254/jphs.FP0060342 (DOI: 10.1254/jphs.FP0060342, PubMed: 16990703)
69.	Yasuhisa Kanematsu, Koichiro Tsuchiya, Hideki Onishi, Yuki Motobayashi, Yuki Izawa, Manabu Ishihara, Keisuke Ishizawa, Shinji Abe, Kazuyoshi Kawazoe and Toshiaki Tamaki : Effects of angiotensin II type 1 receptor blockade on the systemic blood nitric oxide dynamics in Nω-nitro-L-arginine methyl ester-treated rats, Hypertension Research, Vol.29, No.5, 369-374, 2006. (要約) We previously succeeded in measuring the nitrosylhemoglobin (HbNO) level as an index of blood nitric oxide (NO) by the electron paramagnetic resonance (EPR) HbNO signal subtraction method. In this study, we examined the effects of olmesartan, an angiotensin II type 1 receptor blocker (ARB), on NO dynamics in N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated rats by the EPR-subtraction method. Oral administration of L-NAME for 2 weeks induced serious hypertension, and the HbNO concentration was reduced to 37.6% of the level in controls. Coadministration of olmesartan improved hypertension and increased the blood HbNO concentration of L-NAME-treated rats. In contrast, coadministration of hydralazine improved hypertension but did not affect the blood HbNO concentration. In conclusion, our findings suggested that chronic administration of olmesartan ameliorated the endothelial dysfunction in L-NAME-treated rats. (キーワード) Angiotensin II Type 1 Receptor Blockers / Animals / Antihypertensive Agents / Blood Pressure / Body Weight / Electron Spin Resonance Spectroscopy / Endothelium, Vascular / Heart Rate / Hemodynamics / Hemoglobins / Hydralazine / Hypertension / Imidazoles / Male / NG-Nitroarginine Methyl Ester / Nitric Oxide / Rats / Rats, Sprague-Dawley / Tetrazoles (出版サイトへのリンク) ● Publication site (DOI): 10.1291/hypres.29.369 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16832158 ● Search Scopus @ Elsevier (PMID): 16832158 ● Search Scopus @ Elsevier (DOI): 10.1291/hypres.29.369 (DOI: 10.1291/hypres.29.369, PubMed: 16832158)
70.	Yoshiko Fujita, Masanori Yoshizumi, Yuki Izawa, Nermin Ali, Yasuhisa Kanematsu, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Transactivation of fetal liver kinase-1/kinase-insert domain-containing receptor by lysophosphatidylcholine induces vascular endothelial cell proliferation., Endocrinology, Vol.147, No.3, 1377-1385, 2006. (要約) Lysophosphatidylcholine (LPC), a major lipid component of oxidized low-density lipoprotein, is a bioactive lipid molecule involved in numerous biological processes including the progression of atherosclerosis. Recently orphan G protein-coupled receptors were identified as high-affinity receptors for LPC. Although several G protein-coupled receptor ligands transactivate receptor tyrosine kinases, LPC-stimulated transactivation of receptor tyrosine kinase has not yet been reported. Here we observed for the first time that LPC treatment of human umbilical vein endothelial cells (HUVECs) induces tyrosyl phosphorylation of vascular endothelial growth factor receptor 2 [fetal liver kinase-1/kinase-insert domain-containing receptor, Flk-1/KDR)]. Flk-1/KDR transactivation by LPC was inhibited by vascular endothelial growth factor receptor tyrosine kinase inhibitors, SU1498 and 4-[(4'-chloro-2'-fluoro) phenylamino]6,7-dimethoxyquinazoline (VTKi) in immunoprecipitation. Furthermore, we examined the effects of the Src family kinases inhibitors, herbimycin A and 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2), on LPC-induced Flk-1/KDR transactivation. Results from Western blots, c-Src is involved in LPC-induced Flk-1/KDR transactivation because herbimycin A and PP2 inhibited this transactivation. Kinase-inactive (KI) Src transfection also inhibited LPC-induced Flk-1/KDR transactivation. In addition, results from Western blots, ERK1/2 and Akt, which are downstream effectors of Flk-1/KDR, were also activated by LPC, and this was inhibited by SU1498, VTKi, herbimycin A, PP2, and KI Src transfection in HUVECs. LPC-induced stimulation of HUVEC proliferation was shown to be secondary to transactivation because it was suppressed by SU1498, VTKi, herbimycin A, PP2, and KI Src transfection in dimethylthiazoldiphenyltetra-zoliumbromide assay. These findings suggest that LPC-induced Flk-1/KDR transactivation via c-Src may have important implications for the progression of atherosclerosis. (キーワード) 動脈硬化 (atherosclerosis) / Benzoquinones / Blotting, Western / Cell Line / Cell Proliferation / Cell Survival / Cells, Cultured / Cinnamates / Disease Progression / Endothelial Cells / Endothelium, Vascular / Humans / Immunoblotting / Immunoprecipitation / Lactams, Macrocyclic / Ligands / Lysophosphatidylcholines / リン酸化 (phosphorylation) / Protein Structure, Tertiary / Protein-Tyrosine Kinases / Pyrimidines / Quinazolines / Quinones / Transcriptional Activation / Transfection / Vascular Endothelial Growth Factor Receptor-2 (出版サイトへのリンク) ● Publication site (DOI): 10.1210/en.2005-0644 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16322069 ● Summary page in Scopus @ Elsevier: 2-s2.0-32644452665 (DOI: 10.1210/en.2005-0644, PubMed: 16322069, Elsevier: Scopus)
71.	Shuji Kondo, Maki Shimizu, Maki Urushihara, Koichiro Tsuchiya, Masanori Yoshizumi, Toshiaki Tamaki, Akira Nishiyama, Hiroshi Kawachi, Fujio Shimizu, Quinn T. Mark, Lambeth J. David and Shoji Kagami : Addition of the antioxidant probucol to angiotensin II type I receptor antagonist arrests progression mesangioproliferative glomerulonephritis in the rat, Journal of the American Society of Nephrology, Vol.17, No.3, 783-794, 2006. (要約) Angiotensin II (Ang II) and reactive oxidative species (ROS) that are produced by NADPH oxidase have been implicated in the progression of glomerulonephritis (GN). This study examined the effect of simultaneously interrupting Ang II and ROS with an Ang II receptor blocker (ARB), candesartan, and a free radical scavenger, probucol, in a model of progressive mesangioproliferative GN induced by the injection of anti-Thy-1 antibody into uninephrectomized rats. Nephritic rats were divided into four groups and given daily oral doses of the following: Vehicle, 1% probucol diet, 70 mg/L candesartan in drinking water, and probucol plus candesartan. These treatments lasted until day 56. Vehicle-treated nephritic rats developed progressively elevated proteinuria and glomerulosclerosis. Candesartan kept proteinuria significantly lower than vehicle or probucol. The addition of probucol to candesartan normalized urinary protein excretion. Increases in BP in nephritic rats were lowered by these treatments, except with probucol. It is interesting that both glomerular cell number and glomerulosclerosis were significantly decreased by candesartan and normalized by the addition of probucol. Immunohistochemical studies for TGF-beta1, collagen type I, and fibronectin revealed that the combined treatment abolished glomerular fibrotic findings compared with candesartan. In addition, glomerular expression of NADPH oxidase components and superoxide production suggested that the combined treatment completely eliminated NADPH oxidase-associated ROS production. In conclusion, our study provides the first evidence that the antioxidant probucol, when added to an Ang II receptor blockade, fully arrests proteinuria and disease progression in GN. Furthermore, the data suggest that NADPH oxidase-associated ROS production may play a pivotal role in the progression of GN. The combination of probucol and candesartan may represent a novel route of therapy for patients with progressive GN. (キーワード) Angiotensin II Type 1 Receptor Blockers / Animals / Antioxidants / Biopsy, Needle / Blotting, Western / Disease Models, Animal / Disease Progression / Drug Therapy, Combination / Female / Glomerulonephritis, Membranoproliferative / Immunohistochemistry / Male / Probability / Probucol / Proteinuria / Rats / Rats, Sprague-Dawley / Sensitivity and Specificity (出版サイトへのリンク) ● Publication site (DOI): 10.1681/ASN.2005050519 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16467449 ● Search Scopus @ Elsevier (PMID): 16467449 ● Search Scopus @ Elsevier (DOI): 10.1681/ASN.2005050519 (DOI: 10.1681/ASN.2005050519, PubMed: 16467449)
72.	Yoshiko Fujita, Yuki Izawa, Nermin Ali, Koichiro Tsuchiya, Shuichi Hamano, Toshiaki Tamaki and Masanori Yoshizumi : Pramipexole protects against H2O2-induced PC12 cell death, Naunyn-Schmiedeberg's Archives of Pharmacology, Vol.372, No.4, 257-266, 2006. (要約) Pramipexole, a novel non-ergot dopamine (DA) agonist, has been successfully applied to the treatment of Parkinson's disease (PD). Although the specific cause of PD remains unknown, recent studies have provided evidence that oxidative stress plays a role in the parthenogenesis of the disease. In the present study, we examined the effect of pramipexole on hydrogen peroxide (H2O2, 100 microM)-induced PC12 cell death, and the intracellular mechanism of this effect. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay revealed that pretreatment of PC12 cells with pramipexole (1-100 microM) resulted in significant protection against H2O2-induced cell death in a concentration-dependent manner. The protective effect of pramipexole was not affected by pretreatment with the DA receptor antagonists sulpiride, spiperone or domperidone, suggesting that the effect of pramipexole is not mediated by DA receptors. In PC12 cells, pramipexole inhibited H2O2-induced lactate dehydrogenase (LDH) leakage, as well as H2O2-induced cytochrome c release and caspase-3 activation with the resultant apoptosis. It was also observed in PC12 cells that H2O2 stimulated phosphorylation of mitogen-activated protein (MAP) kinases, i.e., extracellular signal-regulated kinase1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase. Pramipexole inhibited H2O2-induced JNK and p38 MAP kinase, but not ERK1/2 phosphorylation. Furthermore, in these cells experiments with a fluorescent probe, 2-[6-(4'-amino)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid, revealed that pramipexole, the JNK inhibitor SP600125 and the p38 MAP kinase inhibitor SB203580 inhibited the generation of H2O2-induced reactive oxygen species. Caspase inhibitors Z-DEVD-FMK and Z-IETD-FMK, as well as SP600125 and SB203580, inhibited H2O2-induced PC12 cell death to a similar extent as pramipexole. These results suggest that pramipexole exerts a protective effect against oxidative stress-induced PC12 cell death in part through an inhibition of JNK and p38 MAP kinase. (キーワード) Animals / Antiparkinson Agents / アポトーシス (apoptosis) / Benzothiazoles / Caspase 3 / Caspases / 細胞死 (cell death) / Cell Survival / Cytochromes c / Dopamine Agonists / Dopamine Antagonists / 過酸化水素水 (hydrogen peroxide) / L-Lactate Dehydrogenase / Mitogen-Activated Protein Kinases / Neuroprotective Agents / 酸化ストレス (oxidative stress) / PC12 Cells / Rats / Thiazoles (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s00210-005-0025-2 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16362428 ● Summary page in Scopus @ Elsevier: 2-s2.0-31144433876 (DOI: 10.1007/s00210-005-0025-2, PubMed: 16362428, Elsevier: Scopus)
73.	Hiroyuki Sakakibara, Kaori Ishida, Yuki Izawa, Yuko Minami, Satomi Saito, Yoshichika Kawai, Veronika Butterweck, Toshiaki Tamaki, Yutaka Nakaya and Junji Terao : Effects of forced swimming stress on rat brain function, The Journal of Medical Investigation : JMI, Vol.52, No.Suppl., 300-3001, 2005. (要約) Chronic stress has been reported to be an essential factor for depression. In this study, the effect of forced swimming stress on neurotransmitters and cellular signaling pathway contributing to brain functions was investigated using the forced swimming test (FST) in order to understanding of mechanisms to regulate stress signals in brain. Antidepressant drug, imipramine, significantly reduced the immobility time of male rats in the FST by 85% at a dose of 15 mg/kg for 2 weeks. This result indicated that the swimming stress caused a depressed state in the rats without administration of imipramine. Swimming stress significantly lowered the serotonergic ratio and also markedly enhanced the phosphorylation of ERK1/2 in the hypothalamus region compared to the rats without FST. These phenomena may be included in key mechanisms of the development of depression. (キーワード) Animals / Antidepressive Agents, Tricyclic / 脳 (brain) / Chromatography, High Pressure Liquid / Enzyme Activation / Hippocampus / Hydroxyindoleacetic Acid / Imipramine / Immunoblotting / Male / Mitogen-Activated Protein Kinase 3 / Motor Activity / リン酸化 (phosphorylation) / Rats / Rats, Inbred Strains / Serotonin / シグナル伝達 (signal transduction) / Stress, Physiological / Swimming / Time Factors (徳島大学機関リポジトリ) ● Metadata: 111587 (出版サイトへのリンク) ● Publication site (DOI): 10.2152/jmi.52.300 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16366521 ● Search Scopus @ Elsevier (PMID): 16366521 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.52.300 (徳島大学機関リポジトリ: 111587, DOI: 10.2152/jmi.52.300, PubMed: 16366521)
74.	田島壮一郎, 土屋浩一郎, 大西秀樹, 兼松康久, 玉置俊晃, Ronald Mason, 滝口祥令 : ラジカル認識抗体を用いた酸化ストレス由来プロテインラジカル検出法, 日本薬理学雑誌, Vol.126, No.4, 246-249, 2005年. (キーワード) 酸化ストレス / ラジカル / ミオグロビン / チオレドキシン (出版サイトへのリンク) ● Publication site (DOI): 10.1254/fpj.126.246 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16327204 ● Search Scopus @ Elsevier (PMID): 16327204 ● Search Scopus @ Elsevier (DOI): 10.1254/fpj.126.246 (DOI: 10.1254/fpj.126.246, PubMed: 16327204)
75.	Koichiro Tsuchiya, Kaori Akai, Akira Tokumura, Shinji Abe, Toshiaki Tamaki, Yoshiharu Takiguchi and Kenji Fukuzawa : Oxygen radical photo-induced by ferric nitrilotriacetate complex, Biochimica et Biophysica Acta (BBA) - General Subjects, Vol.1725, No.1, 111-119, 2005. (要約) This study examined the photo-induced generation of reactive oxygen species (ROS) by the carcinogenic iron(III)-NTA complex. Iron(III)-NTA complex (1:1) has three conformations (type (a) in acidic conditions of pH 1-6, type (n) in neutral conditions of pH 3-9, and type (b) in basic conditions of pH 7-10) with two pK(a) values (pK(a1) approximately 4, pK(a2) approximately 8). The iron(III)-NTA complex was reduced to iron(II) under cool-white fluorescent light without the presence of any reducing agent, and the reduction rates of the three conformations of iron(III)-NTA were in the order type (a)>type (n)>type (b) as reported previously (Akai K. et al., Free Radic. Res. 38, 951-962, 2004). ROS generation was investigated by electron paramagnetic resonance (EPR) spectroscopy with a spin-trapping technique. Apparent EPR signals attributed to PBN/(13)CH(3) and PBN/OCH(3) spin adducts were observed after incubation of the iron(III)-NTA complex was mixed with alpha-phenyl-tert-butylnitrone (PBN) and (13)C-DMSO in an aerobic condition. The addition of catalase effectively attenuated the PBN adducts, but superoxide dismutase enhanced them. Taken together, these results indicate that the iron(III)-NTA complex is spontaneously reduced to the iron(II)-NTA complex by light under acidic to neutral pH, and in turn transfers an electron to molecular oxygen to form ROS. (キーワード) Catalase / Cyclic N-Oxides / Electron Spin Resonance Spectroscopy / Ferric Compounds / Free Radicals / Light / Nitrilotriacetic Acid / Nitrogen Oxides / Oxygen / Photochemistry / Superoxide Dismutase / Time Factors (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.bbagen.2005.05.001 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15950386 ● Search Scopus @ Elsevier (PMID): 15950386 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbagen.2005.05.001 (DOI: 10.1016/j.bbagen.2005.05.001, PubMed: 15950386)
76.	Yuki Izawa, Masanori Yoshizumi, Keisuke Ishizawa, Yoshiko Fujita, Shuji Kondo, Shoji Kagami, Kazuyoshi Kawazoe, Koichiro Tsuchiya, Shuhei Tomita and Toshiaki Tamaki : ERK1/2 activation by angiotensin II inhibits insulin-induced glucose uptake in vascular smooth muscle cells, Experimental Cell Research, Vol.308, No.2, 291-299, 2005. (要約) Clinical evidence suggests a relationship between hypertension and insulin resistance, and cross-talk between angiotensin II (Ang II) and insulin signaling pathways may take place. We now report the effect of Ang II on insulin-induced glucose uptake and its intracellular mechanisms in vascular smooth muscle cells (VSMC). We examined the translocation of glucose transporter-4 (GLUT-4) and glucose uptake in rat aortic smooth muscle cells (RASMC). Mitogen-activated protein (MAP) kinases and Akt activities, and phosphorylation of insulin receptor substrate-1 (IRS-1) at the serine and tyrosine residues were measured by immunoprecipitation and immunoblotting. As a result, Ang II inhibited insulin-induced GLUT-4 translocation from cytoplasm to the plasma membrane in RASMC. Ang II induced extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) activation and IRS-1 phosphorylation at Ser307 and Ser616. Ang II-induced Ser307 and Ser616 phophorylation of IRS-1 was inhibited by a MEK inhibitor, PD98059, and a JNK inhibitor, SP600125. Ang II inhibition of insulin-stimulated IRS-1 tyrosyl phophorylation and Akt activation were reversed by PD98059 but not by SP600125. Ang II inhibited insulin-induced glucose uptake, which was also reversed by PD98059 but not by SP600125. It is shown that Ang II-induced ERK1/2 activation inhibits insulin-dependent glucose uptake through serine phophorylation of IRS-1 in RASMC. (キーワード) Angiotensin II / Animals / Blood Vessels / Cell Membrane / Cytoplasm / Enzyme Activation / Enzyme Inhibitors / Glucose / Glucose Transporter Type 4 / Hypertension / Insulin / Insulin Receptor Substrate Proteins / Insulin Resistance / JNK Mitogen-Activated Protein Kinases / Male / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Monosaccharide Transport Proteins / Muscle Proteins / Myocytes, Smooth Muscle / Phosphoproteins / Phosphorylation / Protein Transport / Protein-Serine-Threonine Kinases / Proto-Oncogene Proteins / Proto-Oncogene Proteins c-akt / Rats / Rats, Sprague-Dawley / Serine / Tyrosine (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.yexcr.2005.04.028 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15921682 ● Search Scopus @ Elsevier (PMID): 15921682 ● Search Scopus @ Elsevier (DOI): 10.1016/j.yexcr.2005.04.028 (DOI: 10.1016/j.yexcr.2005.04.028, PubMed: 15921682)
77.	Keisuke Ishizawa, Yuki Izawa, Hiroyuki Ito, Chieko Miki, Kayoko Miyama, Yoshiko Fujita, Yasuhisa Kanematsu, Koichiro Tsuchiya, Toshiaki Tamaki, Akira Nishiyama and Masanori Yoshizumi : Aldosterone stimulates vascular smooth muscle cell proliferation via big mitoten-activated protein kinase 1 activation, Hypertension, Vol.46, No.4, 1046-1052, 2005. (要約) The nongenomic effects of aldosterone have been implicated in the pathogenesis of various cardiovascular diseases. Aldosterone-induced nongenomic effects are attributable in part to the activation of extracellular signal-regulated kinase 1/2 (ERK1/2), a classical mitogen-activated protein (MAP) kinase. Big MAP kinase 1 (BMK1), a newly identified MAP kinase, has been shown to be involved in cell proliferation, differentiation, and survival. We examined whether aldosterone stimulates BMK1-mediated proliferation of cultured rat aortic smooth muscle cells (RASMCs). Mineralocorticoid receptor (MR) expression and localization were evaluated by Western blotting analysis and fluorolabeling methods. ERK1/2 and BMK1 activities were measured by Western blotting analysis with the respective phosphospecific antibodies. Cell proliferation was determined by Alamar Blue colorimetric assay. Aldosterone (0.1 to 100 nmol/L) dose-dependently activated BMK1 in RASMCs, with a peak at 30 minutes. To clarify whether aldosterone-induced BMK1 activation is an MR-mediated phenomenon, we examined the effect of eplerenone, a selective MR antagonist, on aldosterone-induced BMK1 activation. Eplerenone (0.1 to 10 micromol/L) dose-dependently inhibited aldosterone-induced BMK1 activation in RASMCs. Aldosterone also stimulated RASMC proliferation, which was inhibited by eplerenone. Aldosterone-mediated phenomena were concluded to be attributable to a nongenomic effect because cycloheximide failed to inhibit aldosterone-induced BMK1 activation. Transfection of dominant-negative MAP kinase/ERK kinase 5 (MEK5), which is an upstream regulator of BMK1, partially inhibited aldosterone-induced RASMC proliferation, which was almost completely inhibited by MEK inhibitor PD98059. In addition to the classical steroid activity, rapid nongenomic effects induced by aldosterone may represent an alternative etiology for vascular diseases such as hypertension. (キーワード) 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Aldosterone / Animals / Calcium-Calmodulin-Dependent Protein Kinases / Cell Proliferation / Cells, Cultured / Cycloheximide / Enzyme Activation / フラボノイド (flavonoids) / Genes, Dominant / MAP Kinase Kinase 5 / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinase 7 / Muscle, Smooth, Vascular / Myocytes, Smooth Muscle / Protein Synthesis Inhibitors / Rats / Receptors, Mineralocorticoid / Spironolactone / Transfection (出版サイトへのリンク) ● Publication site (DOI): 10.1161/01.HYP.0000172622.51973.f5 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16087789 ● Search Scopus @ Elsevier (PMID): 16087789 ● Search Scopus @ Elsevier (DOI): 10.1161/01.HYP.0000172622.51973.f5 (DOI: 10.1161/01.HYP.0000172622.51973.f5, PubMed: 16087789)
78.	Yasumasa Ikeda, Ken-ichi Aihara, Takashi Sato, Masashi Akaike, Masanori Yoshizumi, Yuki Suzaki, Yuki Izawa-Ishizawa, Mitsunori Fujimura, Shunji Hashizume, Midori Kato, Shusuke Yagi, Toshiaki Tamaki, Hirotaka Kawano, Takahiro Matsumoto, Hiroyuki Azuma, Shigeaki Kato and Toshio Matsumoto : Androgen receptor gene knockout male mice exhibit impaired cardiac growth and exacerbation of angiotensin II-induced cardiac fibrosis., The Journal of Biological Chemistry, Vol.280, No.33, 29661-29666, 2005. (要約) Androgen has anabolic effects on cardiac myocytes and has been shown to enhance left ventricular enlargement and function. However, the physiological and patho-physiological roles of androgen in cardiac growth and cardiac stress-induced remodeling remains unclear. We aimed to clarify whether the androgen-nuclear androgen receptor (AR) system contributes to the cardiac growth and angiotensin II (Ang II)-stimulated cardiac remodeling by using systemic AR-null male mice. AR knock-out (ARKO) male mice, at 25 weeks of age, and age-matched wild-type (WT) male mice were treated with or without Ang II stimulation (2.0 mg/kg/day) for 2 weeks. ARKO mice with or without Ang II stimulation showed a significant reduction in the heart-to-body weight ratio compared with those of WT mice. In addition, echocardiographic analysis demonstrated impairments of both the concentric hypertrophic response and left ventricular function in Ang II-stimulated ARKO mice. Western blot analysis of the myocardium revealed that activation of extracellular signal-regulated kinases (ERK) 1/2 and ERK5 by Ang II stimulation were lower in ARKO mice than those of WT mice. Ang II stimulation caused more prominent cardiac fibrosis in ARKO mice than in WT mice with enhanced expression of types I and III collagen and transforming growth factor-beta1 genes and with increased Smad2 activation. These results suggest that, in male mice, the androgen-AR system participates in normal cardiac growth and modulates cardiac adaptive hypertrophy and fibrosis during the process of cardiac remodeling under hypertrophic stress. (キーワード) Angiotensin II / Animals / 血圧 (blood pressure) / Cardiomegaly / DNA-Binding Proteins / 肺線維症 (pulmonary fibrosis) / Heart Rate / Male / Mice / Mice, Inbred C57BL / Mice, Inbred CBA / ノックアウトマウス (knockout mice) / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinase 7 / 心筋 (myocardium) / RNA, Messenger / Receptors, Androgen / Smad2 Protein / Trans-Activators / Transforming Growth Factor beta / Transforming Growth Factor beta1 / Ventricular Remodeling (出版サイトへのリンク) ● Publication site (DOI): 10.1074/jbc.M411694200 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15961403 ● Search Scopus @ Elsevier (PMID): 15961403 ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M411694200 (DOI: 10.1074/jbc.M411694200, PubMed: 15961403)
79.	Ali Nermin, Masanori Yoshizumi, Yoshiko Fujita, Yuki Izawa, Yasuhisa Kanematsu, Keisuke Ishizawa, Koichiro Tsuchiya, Seiji Yano, Saburo Sone and Toshiaki Tamaki : A Novel Src Kinase Inhibitor, M475271, Inhibits VEGF-Induced Human Umbilical Vein Endothelial Cell Proliferation and Migration, Journal of Pharmacological Sciences, Vol.98, No.2, 130-141, 2005. (要約) Vascular endothelial growth factor (VEGF) was reported to be a potent proangiogenic factor that plays a pivotal role in both physiological and pathological angiogenesis. M475271, 4-quinazolinamine, N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl) methoxy]-(9Cl), is a new anilinoquinazoline derivative that showed selective inhibition of Src kinase activity and tumor growth in vivo. Here, we examined the effect of M475271 on VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation and migration and their intracellular mechanisms. Our findings showed that M475271 pretreatment resulted in a significant inhibition of VEGF-induced HUVEC proliferation, [(3)H]thymidine incorporation, and migration. M475271 inhibited VEGF-induced Flk-1 and Src phosphorylation and their association. Confocal laser microscopic examination confirmed the inhibitory effect of M475271 on VEGF-induced Flk-1/Src association. M475271 inhibited VEGF-induced extracellular signal-regulated kinase1/2 (ERK1/2) and p38 but not Akt activation in a concentration-dependent manner. M475271, PI3-K inhibitor, and p38 inhibitor inhibited VEGF-induced HUVEC proliferation and migration. However, a MEK1/2 inhibitor inhibited VEGF-induced proliferation but not migration. These findings suggest that M475271 attenuates VEGF-induced HUVEC proliferation and migration through the inhibition of signaling pathways involving Src, ERK1/2, and/or p38. Taken together, these data indicate that M475271 may be a useful candidate for inhibition of endothelial cell proliferation and migration relevant to angiogenesis. (キーワード) M475271 / vascular endothelial growth factor / human umbilical vein endothelial cell proliferation and migration / angiogenesis (出版サイトへのリンク) ● Publication site (DOI): 10.1254/jphs.FP0040850 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15937404 ● Search Scopus @ Elsevier (PMID): 15937404 ● Search Scopus @ Elsevier (DOI): 10.1254/jphs.FP0040850 (DOI: 10.1254/jphs.FP0040850, PubMed: 15937404)
80.	Koichiro Tsuchiya, Yasuhisa Kanematsu, Masanori Yoshizumi, Hideki Ohnishi, Kazuyoshi Kirima, Yuki Izawa, Michiyo Shikishima, Tatsuhiro Ishida, Shuji Kondo, Shoji Kagami, Yoshiharu Takiguchi and Toshiaki Tamaki : Nitrite is an alternative source of NO in vivo, American Journal of Physiology, Heart and Circulatory Physiology, Vol.288, No.5, H2163-H2170, 2005. (要約) In this study, we investigated whether orally administered nitrite is changed to NO and whether nitrite attenuates hypertension in a dose-dependent manner. We utilized a stable isotope of [15N]nitrite (15NO2-) as a source of nitrite to distinguish between endogenous nitrite and that exogenously administered and measured hemoglobin (Hb)-NO as an index of circulating NO in whole blood using electron paramagnetic resonance (EPR) spectroscopy. When 1 mg/kg Na15NO2 was orally administered to rats, an apparent EPR signal derived from Hb15NO (A(Z) = 23.4 gauss) appeared in the blood. The peak blood HbNO concentration occurred at the first measurement after intake (5 min) for treatment with 1 and 3 mg/kg (HbNO: 4.93 +/- 0.52 and 10.58 +/- 0.40 microM, respectively) and at 15 min with 10 mg/kg (HbNO: 38.27 +/- 9.23 microM). In addition, coadministration of nitrite (100 mg/l drinking water) with N(omega)-nitro-L-arginine methyl ester (L-NAME; 1 g/l) for 3 wk significantly attenuated the L-NAME-induced hypertension (149 +/- 10 mmHg) compared with L-NAME alone (170 +/- 13 mmHg). Furthermore, this phenomenon was associated with an increase in circulating HbNO. Our findings clearly indicate that orally ingested nitrite can be an alternative to L-arginine as a source of NO in vivo and may explain, at least in part, the mechanism of the nitrite/nitrate-rich Dietary Approaches to Stop Hypertension diet-induced hypotensive effects. (キーワード) 一酸化窒素 (nitric oxide) / hypertension / 電子スピン共鳴 (electron paramagnetic resonance) (出版サイトへのリンク) ● Publication site (DOI): 10.1152/ajpheart.00525.2004 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15626692 ● Search Scopus @ Elsevier (PMID): 15626692 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpheart.00525.2004 (DOI: 10.1152/ajpheart.00525.2004, PubMed: 15626692)
81.	Akira Nishiyama, Li Yao, Yuyan Fan, Moe Kyaw, Noriyuki Kataoka, Ken Hashimoto, Yukiko Nagai, Emi Nakamura, Masanori Yoshizumi, Takatomi Shokoji, Shoji Kimura, Hideyasu Kiyomoto, Katsuhiko Tsujioka, Masakazu Kohno, Toshiaki Tamaki, Fumihiko Kajiya and Youichi Abe : Involvement of aldosterone and mineralocorticoid receptors in rat mesangial cell proliferation and deformability., Hypertension, Vol.45, No.4, 710-716, 2005. (要約) We demonstrated recently that chronic administration of aldosterone to rats induces glomerular mesangial injury and activates mitogen-activated protein kinases including extracellular signal-regulated kinases 1/2 (ERK1/2). We also observed that the aldosterone-induced mesangial injury and ERK1/2 activation were prevented by treatment with a selective mineralocorticoid receptor (MR) antagonist, eplerenone, suggesting that the glomerular mesangium is a potential target for injuries induced by aldosterone via activation of MR. In the present study, we investigated whether MR is expressed in cultured rat mesangial cells (RMCs) and involved in aldosterone-induced RMC injury. MR expression and localization were evaluated by Western blotting analysis and fluorolabeling methods. Cell proliferation and micromechanical properties were determined by [3H]-thymidine uptake measurements and a nanoindentation technique using an atomic force microscope cantilever, respectively. ERK1/2 activity was measured by Western blotting analysis with an anti-phospho-ERK1/2 antibody. Protein expression and immunostaining revealed that MR was abundant in the cytoplasm of RMCs. Aldosterone (1 to 100 nmol/L) dose-dependently activated ERK1/2 in RMCs with a peak at 10 minutes. Pretreatment with eplerenone (10 micromol/L) significantly attenuated aldosterone-induced ERK1/2 phosphorylation. Aldosterone (100 nmol/L) treatment for 30 hours increased [3H]-thymidine incorporation and decreased the elastic modulus, indicating cellular proliferative and deforming effects of aldosterone, respectively. These aldosterone-induced changes in cellular characteristics were prevented by pretreatment with eplerenone or an ERK (MEK) inhibitor, PD988059 (100 micromol/L). The results indicate that aldosterone directly induces RMC proliferation and deformability through MR and ERK1/2 activation, which may contribute to the pathogenesis of glomerular mesangial injury. (キーワード) mineralocorticoids / aldosterone (出版サイトへのリンク) ● Publication site (DOI): 10.1161/01.HYP.0000154681.38944.9a (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15699469 ● Search Scopus @ Elsevier (PMID): 15699469 ● Search Scopus @ Elsevier (DOI): 10.1161/01.HYP.0000154681.38944.9a (DOI: 10.1161/01.HYP.0000154681.38944.9a, PubMed: 15699469)
82.	Masumi Okamoto, Koichiro Tsuchiya, Yasuhisa Kanematsu, Yuki Izawa, Masanori Yoshizumi, Susumu Kagawa and Toshiaki Tamaki : Nitrite-derived nitric oxide formation following ischemia-reperfusion injyury in kidney., American Journal of Physiology, Renal Physiology, Vol.288, No.1, 182-187, 2005. (要約) Nitric oxide (NO) is synthesized from l-arginine by nitric oxide synthase (NOS), and nitrite and nitrate are believed to be waste forms of NO. We previously reported an enzyme-independent pathway of NO generation from nitrite in acidic conditions. In this study, we show nitrite-derived NO formation in renal ischemia-reperfusion injury using electron paramagnetic resonance (EPR) spectroscopy. In this experiment, we utilized a stable isotope of [(15)N]nitrite as a source of nitrite to distinguish l-arginine-derived NO from [(15)N]nitrite-derived (15)NO. Intravenous infusion of a stable isotope of [(15)N]nitrite ((15)NO(2)(-)) facilitated the formation of Hb(15)NO during renal ischemia, which demonstrated that the origin of NO was nitrite. The EPR signal of Hb(15)NO in kidney appeared after 40 min of renal ischemia, and renal reperfusion decreased the Hb(15)NO level in the kidney and increased it in blood by contrast. In addition, the amount of HbNO was nitrite concentration dependent, and this formation was NOS independent. Our findings suggest that nitrite can be an alternative source of NO in ischemic kidney and that it binds with hemoglobin and then is spread by the circulation after reperfusion. (キーワード) Animals / Electron Spin Resonance Spectroscopy / Hemoglobins / Kidney / Male / 一酸化窒素 (nitric oxide) / Nitric Oxide Synthase / Nitrites / Rats / Rats, Sprague-Dawley / Reperfusion Injury (出版サイトへのリンク) ● Publication site (DOI): 10.1152/ajprenal.00036.2004 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15367387 ● Search Scopus @ Elsevier (PMID): 15367387 ● Search Scopus @ Elsevier (DOI): 10.1152/ajprenal.00036.2004 (DOI: 10.1152/ajprenal.00036.2004, PubMed: 15367387)
83.	Koichiro Tsuchiya, Yoshiharu Takiguchi, Masumi Okamoto, Yuki Izawa, Yasuhisa Kanematsu, Masanori Yoshizumi and Toshiaki Tamaki : Malfunction of vascular control in lifestyle-related diseases : formation of systemic hemoglobin-nitric oxide Complex(HbNO) From Dietary Nitrite, Journal of Pharmacological Sciences, Vol.96, No.4, 395-400, 2004. (要約) Nitric oxide (NO) has many physiological functions. It is believed to be produced from L-arginine by nitric oxide synthase (NOS), and nitrite and nitrate are waste forms of it. By the way, nitrate and nitrite are abundant in vegetables and fruits, especially leafy vegetables and pickled vegetables. Orally-ingested nitrate is changed to nitrite by micro-organelles living in the hypopharynx area, and nitrite is expected to change to NO in the stomach due to its low pH. Indeed, some researchers reported that NO is produced in the gastric cavity, although few reports mentioned the physiological meanings of this NO formation. Therefore, we investigated whether the nitrite-derived NO can shift to the circulation and acts like NOS-derived NO does in tissues. We adopted a stable isotope of nitrite (15NO2-) in order to distinguish between the endogenous nitrite and the exogenously administered one and measured nitrosyl hemoglobin (HbNO) as an index of circulating NO using electron paramagnetic resonance spectroscopy. It appeared that the oral administration of 15N-nitrite formed the Hb15NO in rat blood and decreased the blood pressure of chronic L-NAME treated rats. Our findings suggest that the intake of nitrite (or nitrate)-rich foods such as vegetables and fruits would alter the systemic HbNO dynamism, resulting in the improvement of cardiovascular diseases. (キーワード) nitric oxide(NO) / hemoglobin-NO adduct / electron paramagnetic resonance / nitrite (出版サイトへのリンク) ● Publication site (DOI): 10.1254/jphs.FMJ04006X3 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15599101 ● Search Scopus @ Elsevier (PMID): 15599101 ● Search Scopus @ Elsevier (DOI): 10.1254/jphs.FMJ04006X3 (DOI: 10.1254/jphs.FMJ04006X3, PubMed: 15599101)
84.	Kaori Akai, Koichiro Tsuchiya, Akira Tokumura, Kentaro Kogure, Satoru Ueno, Akira Shibata, Toshiaki Tamaki and Kenji Fukuzawa : Ability of ferric nitrilotriacetate complex with three pH-dependent conformations to induce lipid peroxidation., Free Radical Research, Vol.38, No.9, 951-962, 2004. (出版サイトへのリンク) ● Publication site (DOI): 10.1080/1071576042000261945 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15621713 ● Search Scopus @ Elsevier (PMID): 15621713 ● Search Scopus @ Elsevier (DOI): 10.1080/1071576042000261945 (DOI: 10.1080/1071576042000261945, PubMed: 15621713)
85.	Moe Kyaw, Masanori Yoshizumi, Koichiro Tsuchiya, Yuki Izawa, Yasuhisa Kanematsu, Yoshiko Fujita, Nermin Ali, Keisuke Ishizawa, Aiko Yamauchi and Toshiaki Tamaki : Antioxidant effects of stereoisomers of N-acetylcysteine (NAC), L-NAC and D-NAC, on angiotensin II-stimulated MAP kinase activation and vascular smooth muscle cell proliferation, Journal of Pharmacological Sciences, Vol.95, No.4, 483-486, 2004. (要約) We examined the effects of the stereoisomers of N-acetylcysteine (NAC), L-NAC and D-NAC, on cellular glutathione (GSH) concentration and whether NAC-regulated cellular GSH levels are directly associated with angiotensin II (Ang II)-induced intracellular signaling events in vascular smooth muscle cells (VSMC). Both L-NAC and D-NAC similarly increased intracellular GSH concentration. We found that L-NAC and D-NAC both inhibited Ang II-induced c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and [(3)H]-thymidine incorporation in VSMC. Our present study indicates the comparable effects of NAC stereoisomers in regulating intracellular GSH and the redox-dependent intracellular signaling mechanisms in VSMC. (キーワード) Acetylcysteine / Angiotensin II / Animals / Antioxidants / Aorta, Thoracic / Cell Proliferation / Enzyme Activation / Glutathione / JNK Mitogen-Activated Protein Kinases / Male / Mitogen-Activated Protein Kinases / Muscle, Smooth, Vascular / Myocytes, Smooth Muscle / Rats / Rats, Sprague-Dawley / Signal Transduction / Stereoisomerism / Thymidine / p38 Mitogen-Activated Protein Kinases (出版サイトへのリンク) ● Publication site (DOI): 10.1254/jphs.SC0040061 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15297771 ● Search Scopus @ Elsevier (PMID): 15297771 ● Search Scopus @ Elsevier (DOI): 10.1254/jphs.SC0040061 (DOI: 10.1254/jphs.SC0040061, PubMed: 15297771)
86.	Moe Kyaw, Masanori Yoshizumi, Koichiro Tsuchiya, Yuki Izawa, Yasuhisa Kanematsu and Toshiaki Tamaki : Atheroprotective effects of antioxidants through inhibition of mitogen-activated protein kinases, Acta Pharmacologica Sinica, Vol.25, No.8, 977-985, 2004. (要約) Reactive oxygen species (ROS) have been known to play an important role in the pathogenesis of atherosclerosis and several other cardiovascular diseases. It is now apparent that ROS induce endothelial cell damage and vascular smooth muscle cell (VSMC) growth and cardiac remodeling, which are associated with hypertension, atherosclerosis, heart failure, and restenosis. Several lines of evidence have indicated that ROS and mitogen-activated protein (MAP) kinases were involved in vascular remodeling under various pathological conditions. Recently, it was also reported that MAP kinases were sensitive to oxidative stress. MAP kinases play an important role in cell differentiation, growth, apoptosis, and the regulation of a variety of transcription factors and gene expressions. Bioflavonoids and polyphenolic compounds are believed to be beneficial for the prevention and treatment of atherosclerosis and cardiovascular diseases. One of the most widely distributed bioflavonoids, 3,3',4',5,7-penta-hydroxyflavone (quercetin) and its metabolite quercetin 3-O-beta-D-glucuronide (Q3GA) inhibited Angiotensin II-stimulated JNK activation and resultant hypertrophy of VSMC. Several studies have suggested that various antioxidants including probucol, N-acetyl-L-cysteine, diphenylene iodonium, Trolox C (vitamin E analogue), and vitamin C inhibit VSMC growth, which is associated with pathogenesis of cardiovascular diseases. Therefore, inhibition of MAP kinases by antioxidant treatment may prove to be a therapeutic strategy for cardiovascular diseases. In contrast, some clinical studies have reported that antioxidant vitamins did not show beneficial effects in coronary artery disease or in a number of high-risk people. Thus, further studies are needed to clarify why antioxidants showed beneficial effects in vitro, whereas less satisfactory results were obtained in some clinical conditions. (キーワード) 活性酸素 (reactive oxygen species) / mitogen-activated protein kinase / 抗酸化物質 (antioxidant) / vascular smooth muscle cell / 動脈硬化 (atherosclerosis) (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15301727 ● Search Scopus @ Elsevier (PMID): 15301727 (PubMed: 15301727)
87.	Keisuke Ishizawa, Masanori Yoshizumi, Koichiro Tsuchiya, Hitoshi Houchi, Kazuo Minakuchi, Yuki Izawa, Yasuhisa Kanematsu, Shoji Kagami, Masao Hirose and Toshiaki Tamaki : Dual effects of endothelin-1 (1-31): induction of mesangial cell migration and facilitation of monocyte recruitment through monocyte chemoattractant protein-1 production by mesangial cells, Hypertension Research, Vol.27, No.6, 433-440, 2004. (要約) We previously found that human chymase selectively cleaves big endothelin-1 (ET-1) at the Tyr31-Gly32 bond and produces 31-amino acid endothelins, ET-1 (1-31), without any further degradation products. In this study, we investigated the effect of ET-1 (1-31) on the migration of cultured rat mesangial cells (RMCs) and on cells of the human monocytic cell line, THP-1. In addition, we examined the interaction between RMCs and THP-1 cells using conditioned media from ET-1 (1-31)-stimulated RMCs. ET-1 (1-31) caused an increase in RMC migration in a concentration-dependent manner, and the degree of increase was similar to those by ET-1 and angiotensin II (All). The ET-1 (1-31)-induced increase in RMC migration was inhibited by BQ123, an endothelin ETA receptor antagonist, but not by BQ788, an endothelin ETB receptor antagonist. ET-1 (1-31) alone did not cause significant migration of THP-1 cells. However, significant recruitment of THP-1 cells was observed with conditioned media taken from ET-1 (1-31)-stimulated RMCs. The conditioned media-induced migration of THP-1 cells was inhibited by BQ123, but not by BQ788. Western blotting analysis of the lysate of RMCs revealed that the expression of monocyte chemoattractant protein-1 (MCP-1) protein in RMCs was increased by treatment with ET-1 (1-31). The addition of neutralizing antibody for MCP-1 to the medium inhibited the migration of THP-1 cells induced by conditioned media from ET-1 (1-31)-stimulated RMCs. These findings suggest that ET-1 (1-31) play a role in glomerulonephritis (GN) via dual effects that directly cause the migration of mesangial cells (MCs) and may be responsible for the recruitment of mononuclear cells mediated through the activation of MCs. Since human chymase has been reported to be involved in glomerular disease, ET-1 (1-31) may be among the mediators. (キーワード) Animals / Antibodies / Antihypertensive Agents / Cell Movement / Cells, Cultured / Chemokine CCL2 / Culture Media, Conditioned / Endothelin-1 / Glomerular Mesangium / Peptide Fragments / Peptides, Cyclic / Rats / Rats, Sprague-Dawley (出版サイトへのリンク) ● Publication site (DOI): 10.1291/hypres.27.433 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15253109 ● Search Scopus @ Elsevier (PMID): 15253109 ● Search Scopus @ Elsevier (DOI): 10.1291/hypres.27.433 (DOI: 10.1291/hypres.27.433, PubMed: 15253109)
88.	Yuki Suzaki, Masanori Yoshizumi, Shoji Kagami, Akira Nishiyama, Yuichi Ozawa, Moe Kyaw, Yuki Izawa, Yasuhisa Kanematsu, Koichiro Tsuchiya and Toshiaki Tamaki : BMK1 is activated in glomeruli of diabetic rats and in mesangial cells by high glucose conditions, Kidney International, Vol.65, No.5, 1749-1760, 2004. (要約) High glucose causes renal cell injury through various signal transduction pathways, including mitogen-activated protein (MAP) kinases cascades. Big MAP kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a recently identified MAP kinase family member and was reported to be sensitive to osmotic and oxidative stress. However, the role of BMK1 in diabetic nephropathy has not been elucidated yet. We investigated whether BMK1 is activated in the glomeruli of Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus in comparison with the control Long Evans Tokushima Otsuka (LETO) rats. We also examined the effect of high glucose on BMK1 activity in cultured rat mesangial cells. BMK1 and ERK1/2 but not p38 were activated in the glomeruli of OLETF rats, which showed diabetic nephropathy at 52 weeks of age. High glucose, in addition to a high concentration of raffinose, caused rapid and significant activation of BMK1 in rat mesangial cells. MAP kinase/ERK kinase (MEK) inhibitors, U0126 and PD98059, both inhibited BMK1 activation by high glucose in a concentration-dependent manner. Protein kinase C (PKC) inhibition by GF109203X and PKC down-regulation with long-time phorbol myristate acetate (PMA) treatment both inhibited BMK1 and Src kinase activation. Src kinase inhibitors, herbimycin A and PP2, also inhibited high glucose-induced BMK1 activation. PKC inhibitors, Src inhibitors and MEK inhibitors, all inhibited cell proliferation by high glucose. Finally, transfection of dominant-negative MEK5, which is an upstream regulator of BMK1, abolished the BMK1-mediated rat mesangial cell proliferation stimulated by high glucose. In the present study, we demonstrated that high glucose activates BMK1 both in vivo and in vitro. It was suggested that high glucose induces PKC- and c-Src-dependent BMK1 activation. It could not be denied that BMK1 activation is induced through an osmotic stress-sensitive mechanism. BMK1-mediated mesangial cell growth may be involved in the pathogenesis of diabetic nephropathy. (キーワード) Animals / Butadienes / Cells, Cultured / Diabetes Mellitus, Type 2 / Diabetic Nephropathies / Enzyme Activation / Enzyme Inhibitors / Glomerular Mesangium / グルコース (glucose) / MAP Kinase Kinase 5 / Male / Mitogen-Activated Protein Kinase 7 / Nitriles / Organic Chemicals / Protein Kinase C / Protein-Tyrosine Kinases / Rats / Rats, Inbred OLETF (出版サイトへのリンク) ● Publication site (DOI): 10.1111/j.1523-1755.2004.00576.x (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15086914 ● Search Scopus @ Elsevier (PMID): 15086914 ● Search Scopus @ Elsevier (DOI): 10.1111/j.1523-1755.2004.00576.x (DOI: 10.1111/j.1523-1755.2004.00576.x, PubMed: 15086914)
89.	Moe Kyaw, Masanori Yoshizumi, Koichiro Tsuchiya, Shoji Kagami, Yuki Izawa, Yoshiko Fujita, Nermin Ali, Yasuhisa Kanematsu, Kazunori Toida, Kazunori Ishimura and Toshiaki Tamaki : Src and Cas are essentially but differentially involved in angiotensin II-stimulated migration of vascular smooth muscle cell via extracellur signal-regulated kinase 1/2 and c-Jun NH2-terminal kinase activation, Molecular Pharmacology, Vol.65, No.4, 832-841, 2004. (要約) Angiotensin II (Ang II) plays an important role in several cardiovascular diseases associated with vascular smooth muscle cell (VSMC) growth and migration. Src activity is known to be required for the migration of a number of cell types. p130Cas was reported to be essential for cell migration and actin filament reorganization. Mitogen-activated protein (MAP) kinases were also reported to be critical regulatory factors for growth and migration of VSMC. However, precise intracellular mechanisms involving c-Src, p130Cas, and MAP kinases in Ang II-stimulated migration of VSMC have not been well elucidated. Here we demonstrated that Ang II rapidly and significantly stimulated tyrosine phosphorylation of Src and Cas and their association in rat aortic smooth muscle cells (RASMC). Ang II-stimulated tyrosine phosphorylation of Src and Cas and activation of ERK1/2 and JNK, but not p38, were potently inhibited by Src family tyrosine kinase inhibitors, herbimycin A (HA) and PP2. Ang II-stimulated Src and Cas association, tyrosine phosphorylation of Cas, and activation of ERK1/2 and JNK were suppressed in kinase-inactive Src (KI Src)-overexpressed RASMC. Ang II-stimulated JNK activation but not ERK1/2 activation was blocked in substrate domain-deleted Cas (DeltaSD Cas)-overexpressed RASMC. In addition, HA, PP2, ERK1/2 inhibitor, 2'-amino-3'-methoxyflavone (PD98059) and JNK inhibitor, and anthra[1,9-cd]pyrazol-6(2H)-one (SP600125) significantly inhibited Ang II-stimulated migration of RASMC. Ang II-induced colocalization of Src and Cas and migration were inhibited in both KI Src- and DeltaSD Cas-overexpressed RASMC. These findings suggest that Src and Cas are essentially but differentially involved in Ang II-stimulated migration of VSMC through the activation of ERK1/2 and JNK. (キーワード) Angiotensin II / Animals / Cell Adhesion / Cell Movement / Cells, Cultured / Cellular Apoptosis Susceptibility Protein / Enzyme Activation / Genes, src / JNK Mitogen-Activated Protein Kinases / Male / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinases / Muscle, Smooth, Vascular / リン酸化 (phosphorylation) / Rats / Rats, Sprague-Dawley / Tyrosine / Vinculin / src-Family Kinases (出版サイトへのリンク) ● Publication site (DOI): 10.1124/mol.65.4.832 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15044612 ● Search Scopus @ Elsevier (PMID): 15044612 ● Search Scopus @ Elsevier (DOI): 10.1124/mol.65.4.832 (DOI: 10.1124/mol.65.4.832, PubMed: 15044612)
90.	Akira Nishiyama, Masanori Yoshizumi, Matlubur Rahman, Hiroyuki Kobori, DaleM Seth, Akira Miyatake, Guo-Xing Zhang, Li Yao, Hirofumi Hitomi, Takatomi Shokoji, Hideyasu Kiyomoto, Shoji Kimura, Toshiaki Tamaki, Masakazu Kohno and Youichi Abe : Effects of AT1 receptor blockade on renal injury and mitogen-activated protein activity in Dahl salt-sensitive rats, Kidney International, Vol.65, No.3, 972-981, 2004. (要約) The mitogen-activated protein kinase (MAPK) cascade is an important intracellular mediator of angiotensin II (Ang II)-induced cell growth and differentiation. Here, we examined the effect of angiotensin II type 1 receptor (AT1) receptor blockade on renal injury and MAPK activity in Dahl salt-sensitive (DS) rats. DS rats were maintained on a high (H: 8.0%NaCl, N= 8) or low (L: 0.3%NaCl, N= 7) salt diet, or H + candesartan cilexetil (10 to 15 mg/kg/day, N= 8). Urinary protein excretion (UproteinV), renal cortical collagen content, and glomerular injury (assessed by semiquantitative morphometric analysis) were determined after 4-week treatments. Plasma and kidney Ang II levels were measured by radioimmunoassay. Protein levels of AT1 and AT2 receptors in the renal cortical tissues were analyzed by Western-blotting analyses. MAPKs activities, including extracellular signal-regulated kinases (ERK)1/2, c-Jun NH2-terminal kinases (JNK), p38 MAPK, and Big-MAPK-1 (BMK1), were measured by Western-blotting analyses or in vitro kinase assays. DS/H rats showed higher mean blood pressure (MBP), UproteinV, and renal cortical collagen content than DS/L rats. Increased ERK1/2, JNK, and BMK1 activities were observed in renal cortical tissues of DS/H rats (approximately 6.3-, 4.5-, and 2.5-fold, respectively), whereas p38 MAPK activity was unchanged. Plasma Ang II levels were significantly reduced in DS/H rats compared with DS/L rats, whereas kidney Ang II contents and AT1 receptor protein levels were similar. Candesartan did not alter MBP, but significantly reduced UproteinV and collagen content, and ameliorated progressive sclerotic and proliferative glomerular changes. Furthermore, candesartan decreased renal tissue Ang II contents (from 216 +/- 19 to 46 +/- 3 fmol/mL) and ERK1/2, JNK, and BMK1 activities (-45%, -60%, and -70%, respectively) in DS/H rats. In DS hypertensive rats, some of the renoprotective effects of AT1 receptor blockade are accompanied by reductions in intrarenal Ang II contents and MAPK activity, which might not be mediated through arterial pressure changes. (キーワード) Angiotensin II Type 1 Receptor Blockers / Animals / Antihypertensive Agents / Benzimidazoles / Biphenyl Compounds / Blood Pressure / Collagen / Hypertension, Renal / JNK Mitogen-Activated Protein Kinases / Kidney Cortex / MAP Kinase Signaling System / Male / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinase 7 / Mitogen-Activated Protein Kinases / Organ Size / Rats / Rats, Inbred Dahl / Receptor, Angiotensin, Type 1 / Receptor, Angiotensin, Type 2 / Renin / Renin-Angiotensin System / Tetrazoles / p38 Mitogen-Activated Protein Kinases (出版サイトへのリンク) ● Publication site (DOI): 10.1111/j.1523-1755.2004.00476.x (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14871417 ● Search Scopus @ Elsevier (PMID): 14871417 ● Search Scopus @ Elsevier (DOI): 10.1111/j.1523-1755.2004.00476.x (DOI: 10.1111/j.1523-1755.2004.00476.x, PubMed: 14871417)
91.	Masanori Yoshizumi, Yoshiko Fujita, Yuki Izawa, Yuki Suzaki, Moe Kyaw, Nermin Ali, Koichiro Tsuchiya, Shoji Kagami, Seiji Yano, Saburo Sone and Toshiaki Tamaki : Ebselen inhibits tumor necrosis factor-α-induced c-jun N-terminal kinase activation and adhesion molecule expression in endothelial cells, Experimental Cell Research, Vol.292, No.1, 1-10, 2004. (要約) Tumor necrosis factor-alpha (TNF-alpha) stimulates expression of endothelial cell (EC) genes that may promote atherosclerosis in part by an activation of mitogen-activated protein (MAP) kinases. Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one), a selenoorganic compound, is effective for acute ischemic stroke; however, its effect on EC has not yet been elucidated. We examined the effect of ebselen on TNF-alpha-induced MAP kinase activation and adhesion molecule expression in cultured human umbilical vein endothelial cells (HUVEC). Extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 were rapidly and significantly activated by TNF-alpha in HUVEC. TNF-alpha-induced JNK activation was inhibited by ebselen, whereas ERK1/2 and p38 were not affected. Apoptosis signal-regulated kinase 1 (ASK1) was suggested to be involved in TNF-alpha-induced JNK activation because transfection of kinase-inactive ASK1 inhibited TNF-alpha-induced JNK activation. Ebselen inhibited TNF-alpha-induced TNF receptor-associated factor 2 (TRAF2)-ASK1 complex formation and phosphorylation of stress-activated protein kinase ERK kinase 1 (SEK1), which is an upstream signaling molecule of JNK. Finally, TNF-alpha-induced activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) activation and resultant intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions were inhibited by ebselen. Specific inhibitors for JNK and NF-kappaB also inhibited TNF-alpha-induced ICAM-1 and VCAM-1 expressions in HUVEC. These findings suggest that ebselen prevents TNF-alpha-induced EC activation through the inhibition of TRAF2-ASK1-SEK1 signaling pathway, which leads to JNK activation. Inhibition of JNK by ebselen may imply its usefulness for the prevention of atherosclerosis relevant to EC activation. (キーワード) Azoles / Cell Adhesion Molecules / Cells, Cultured / Endothelium, Vascular / Enzyme Activation / Humans / Intercellular Adhesion Molecule-1 / JNK Mitogen-Activated Protein Kinases / MAP Kinase Kinase 4 / Mitogen-Activated Protein Kinase Kinases / Mitogen-Activated Protein Kinases / NF-kappa B / Organoselenium Compounds / Phosphorylation / Time Factors / Transcription Factor AP-1 / Tumor Necrosis Factor-alpha / Umbilical Veins / Vascular Cell Adhesion Molecule-1 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.yexcr.2003.08.003 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14720501 ● CiNii @ 国立情報学研究所 (CRID): 1571980076667609856 ● Search Scopus @ Elsevier (PMID): 14720501 ● Search Scopus @ Elsevier (DOI): 10.1016/j.yexcr.2003.08.003 (DOI: 10.1016/j.yexcr.2003.08.003, PubMed: 14720501, CiNii: 1571980076667609856)
92.	Nermin Ali, Masanori Yoshizumi, Koichiro Tsuchiya, Moe Kyaw, Yoshiko Fujita, Yuki Izawa, Shinji Abe, Yasuhisa Kanematsu, Shoji Kagami and Toshiaki Tamaki : Ebsalen inhibits p38MAP kinase-mediated endothelial cell death by hydrogen peroxide., European Journal of Pharmacology, Vol.485, No.1-3, 127-135, 2004. (要約) Ebselen (2-phenyl-1, 2-benzisoselenazol-3[2H]-one) is a seleno-organic compound exhibiting both glutathione peroxidase and antioxidant activity. Although it has been reported that ebselen is effective against hydrogen peroxide (H(2)O(2))-induced cell death in several cell types, its effect on endothelial cell damage has not yet been elucidated. In the present study, we examined the effect of ebselen on H(2)O(2)-induced human umbilical vein endothelial cells (HUVECs) death, and its intracellular mechanism. Our findings showed that pretreatment of HUVECs with ebselen resulted in a significant recovery from H(2)O(2)-induced cell death in a concentration-dependent manner. In addition to the inhibition of lactate dehydrogenase (LDH) leakage, ebselen inhibited H(2)O(2)-induced cytochrome c release and caspase-3 activation and the resultant apoptosis in HUVECs. Moreover, it was observed that H(2)O(2) significantly stimulated activation of mitogen-activated protein (MAP) kinases, i.e., p38 MAP kinase, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK1/2). Ebselen inhibited H(2)O(2)-induced p38 MAP kinase, but not JNK or ERK1/2 activation. Furthermore, SB203580 (4-[4-fluorophenyl]-2-[4-methylsulfinylphenyl]-5-[4-pyridyl]-1H-imidazole), a specific p38 MAP kinase inhibitor, inhibited H(2)O(2)-induced p38 MAP kinase phosphorylation, cytochrome c release, caspase-3 activation, as well as cell death in HUVECs. These findings suggest that ebselen attenuates H(2)O(2)-induced endothelial cell death through the inhibition of signaling pathways mediated by p38 MAP kinase, caspase-3, and cytochrome c release. Thus, inhibition of p38 MAP kinase by ebselen may imply its usefulness for prevention and/or treatment of endothelial cell dysfunction, which was suggested to be the first step in the development of atherosclerosis. (キーワード) Azoles / 細胞死 (cell death) / Cell Survival / Dose-Response Relationship, Drug / Endothelial Cells / Enzyme Inhibitors / Humans / 過酸化水素水 (hydrogen peroxide) / Mitogen-Activated Protein Kinases / Organoselenium Compounds / p38 Mitogen-Activated Protein Kinases (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.ejphar.2003.11.079 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14757132 ● Search Scopus @ Elsevier (PMID): 14757132 ● Search Scopus @ Elsevier (DOI): 10.1016/j.ejphar.2003.11.079 (DOI: 10.1016/j.ejphar.2003.11.079, PubMed: 14757132)
93.	Shinji Abe, Kazuyoshi Kirima, Koichiro Tsuchiya, Masumi Okamoto, Toyoshi Hasegawa, Hitoshi Houchi, Masanori Yoshizumi and Toshiaki Tamaki : The reaction rate of edaravone ( 3-methyl-1-phenyl-2-pyrazolin-5-one(MCI-186) with hydroxyl radical., Chemical & Pharmaceutical Bulletin, Vol.52, No.2, 186-191, 2004. (要約) The pyrazoline derivative edaravone is a potent hydroxyl radical scavenger that has been approved for attenuation of brain damage caused by ischemia-reperfusion. In the present work, we first determined the rate constant, k(r), at which edaravone scavenges radicals generated by a Fenton reaction in aqueous solution in the presence of the spin trap agent, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which competed with edaravone. We detected the edaravone radicals in the process of hydroxyl radical scavenging and found that edaravone reacts with hydroxyl radical around the diffusion limit (k(r)=3.0 x 10(10) M(-1) s(-1)). The EPR (electron paramagnetic resonance) spectrum of the edaravone radical was observed by oxidation with a horseradish peroxidase-hydrogen peroxide system using the fast-flow method. This radical species is unstable and changed to another radical species with time. In addition, it was found that edaravone consumed molecular oxygen when it was oxidized by horseradish peroxidase (HRP)-H(2)O(2) system, and that edaravone was capable of providing two electrons to the electrophiles. The possible mechanisms for oxidation of edaravone were investigated from these findings. (キーワード) Antipyrine / Cyclic N-Oxides / Electron Spin Resonance Spectroscopy / Free Radical Scavengers / Hydroxyl Radical / Oxidation-Reduction / Spin Trapping (出版サイトへのリンク) ● Publication site (DOI): 10.1248/cpb.52.186 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14758002 ● CiNii @ 国立情報学研究所 (CRID): 1390001204168756992 ● Search Scopus @ Elsevier (PMID): 14758002 ● Search Scopus @ Elsevier (DOI): 10.1248/cpb.52.186 (DOI: 10.1248/cpb.52.186, PubMed: 14758002, CiNii: 1390001204168756992)
94.	Akira Nishiyama, Masanori Yoshizumi, Hirofumi Hitomi, Shoji Kagami, Shuji Kondo, Akira Miyatake, Megumu Fukunaga, Toshiaki Tamaki, Hideyasu Kiyomoto, Masakazu Kohno, Takatomi Shokoji, Shoji Kimura and Abe Youichi : The SOD mimetic tempol ameliorates glomerular injury and reduces MAPK activity in Dahl salt-sensitive rats., Journal of the American Society of Nephrology, Vol.15, No.2, 306-315, 2004. (要約) It was shown recently that renal injury in Dahl salt-sensitive (DS) hypertensive rats is accompanied by mitogen-activated protein kinase (MAPK) activation. The present study was conducted to elucidate the contribution of reactive oxygen species to MAPK activities and renal injury in DS rats. DS rats were maintained on high salt (H; 8.0% NaCl; n = 7) or low salt (L; 0.3% NaCl; n = 6) diets; H + a superoxide dismutase mimetic, tempol (3 mmol/L in drinking water; n = 8); or H + hydralazine (0.5 mmol/L in drinking water; n = 8) for 4 wk. Mean BP (MBP) in DS/H and DS/L rats was 185 +/- 7 and 113 +/- 3 mmHg, respectively. DS/H rats showed a higher ratio of urinary protein excretion and creatinine (U(protein)V/U(cr)V; 20.3 +/- 1.1) and a higher cortical collagen content (22 +/- 1 micro g/mg) than in DS/L rats (2.4 +/- 0.1 and 13 +/- 1 micro g/mg, respectively). The expression of p22-phox and Nox-1, essential components of NAD(P)H oxidase, in renal cortical tissue was approximately threefold higher in DS/H rats than in DS/L rats. Increased activities of renal cortical MAPK, including extracellular signal-regulated kinases (ERK) 1/ERK2 and c-Jun NH(2)-terminal kinases (JNK) were also observed in DS/H rats by 7.0 +/- 0.7- and 4.3 +/- 0.2-fold, respectively. Tempol treatment significantly decreased MBP (128 +/- 3 mmHg), U(protein)V/U(cr)V (4.8 +/- 0.4), and cortical collagen content (14 +/- 1 micro g/mg) and normalized ERK1/ERK2 and JNK activities in DS/H rats. Histologically, tempol markedly ameliorated progressive sclerotic and proliferative glomerular changes in DS/H rats. Hydralazine-treated DS/H rats showed similar MBP (127 +/- 5 mmHg) to tempol-treated DS/H rats. Hydralazine also decreased U(protein)V/U(cr)V (16.2 +/- 1.5) and cortical collagen content (19 +/- 1 micro g/mg) in DS/H rats. However, these values were significantly higher than those of tempol-treated rats. Furthermore, although hydralazine significantly reduced JNK activity (-56 +/- 3%), ERK1/ERK2 activities were unaffected. These data suggest that reactive oxygen species, generated by NAD(P)H oxidase, contribute to the progression of renal injury through ERK1/ERK2 activation in DS/H hypertensive rats. (キーワード) Animals / Collagen / Cyclic N-Oxides / JNK Mitogen-Activated Protein Kinases / Kidney Glomerulus / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinases / Proteinuria / Rats / Rats, Inbred Dahl / Spin Labels / p38 Mitogen-Activated Protein Kinases (出版サイトへのリンク) ● Publication site (DOI): 10.1097/01.ASN.0000108523.02100.E0 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14747377 ● Search Scopus @ Elsevier (PMID): 14747377 ● Search Scopus @ Elsevier (DOI): 10.1097/01.ASN.0000108523.02100.E0 (DOI: 10.1097/01.ASN.0000108523.02100.E0, PubMed: 14747377)
95.	Toyoshi Hasegawa, Atsushi Bando, Koichiro Tsuchiya, Shinji Abe, Masumi Okamoto, Kazuyoshi Kirima, Satoru Ueno, Masanori Yoshizumi, Hitoshi Houchi and Toshiaki Tamaki : Enzymatic and non-enzymatic formation of reactive oxygen species from 6-anilino-5,8-quinolineequinone, Biochimica et Biophysica Acta (BBA) - General Subjects, Vol.1670, No.1, 19-27, 2004. (要約) The nonenzymatic and enzymatic formation of reactive oxygen species (ROS) from LY83583 (6-anilino-5,8-quinolinequinone) was investigated by electron paramagnetic resonance (EPR) spectroscopy. In the presence of thiol compounds such as glutathione and L-cysteine, LY83583 underwent a one-electron reduction due to low redox potential (-0.3+/-0.01 V vs. SCE), followed by formation of LY83583 semiquinone anion radical. This species was characterized by EPR spectroscopy under an argon atmosphere at neutral pH. Under an aerobic condition, this species interacts with molecular oxygen to form a superoxide anion radical. GSH-conjugated LY83583 was also identified by NMR and FAB-MS. When LY83583 was applied to PC12 cells, ROS formation was completely inhibited by both the flavoenzyme inhibitor DPI and the DT-diaphorase inhibitor dicumarol. On the other hand, ROS generation occurred independent of intracellular GSH level. These results indicate that LY83583 can generate ROS both enzymatically and nonenzymatically, although the enzymatic formation is dominant over the nonenzymatic system in PC12 cells. (キーワード) Aminoquinolines / Animals / Chromatography, High Pressure Liquid / Cyclic N-Oxides / Electrochemistry / Electron Spin Resonance Spectroscopy / Enzyme Inhibitors / Glutathione / Glutathione Disulfide / Magnetic Resonance Spectroscopy / Mass Spectrometry / Molecular Structure / Oxygen Consumption / PC12 Cells / Rats / Reactive Oxygen Species / Spin Trapping (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.bbagen.2003.10.008 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14729138 ● Search Scopus @ Elsevier (PMID): 14729138 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbagen.2003.10.008 (DOI: 10.1016/j.bbagen.2003.10.008, PubMed: 14729138)
96.	Koichiro Tsuchiya, Kazuyoshi Kirima, Masanori Yoshizumi and Toshiaki Tamaki : New methods to evaluate endotherial function: Evaluation of endotherial function by hemoglobin-nitric oxide complex using electron paramagnetic resonance spectroscopy, Journal of Pharmacological Sciences, Vol.93, No.4, 417-422, 2003. (要約) This minireview describes the practical use of assay systems to detect nitric oxide (NO) by electron paramagnetic resonance (EPR) spectroscopy for evaluation of endothelial functions. The iron(II)-dithiocarbamate complexes, such as iron(II)-(N-methyl-D-glucamine dithiocarbamate), are commonly used in EPR detection of NO both in vivo and in vitro. However, due to their redox activity, these complexes have some drawbacks that limit their usefulness for the detection of NO. On the other hand, the measurement of hemoglobin-NO adduct (HbNO) in whole blood by the EPR method seems relevant for the assessment of systemic NO levels. However, ceruloplasmin and an unknown radical species overlapping the same magnetic field as that of HbNO, which makes it physically impossible to measure small amounts of HbNO. Thus, to reveal the EPR spectrum of HbNO, we developed the EPR signal subtraction method, which is based on the computer-assisted subtraction of the digitized EPR spectrum of HbNO-depleted blood from that of the sample blood using software. Using this technique, we succeeded in measuring the steady blood HbNO level as an index of NO by the EPR HbNO signal subtraction method. We also demonstrated that temocapril reduces abnormalities of NO dynamics in the L-NAME (N(omega)-nitro-L-arginine-methylester)-induced endothelial dysfunction of rats using the EPR HbNO signal subtraction method. (キーワード) Animals / Electron Spin Resonance Spectroscopy / Endothelium, Vascular / Ferrous Compounds / Hemoglobin A, Glycosylated / Nitric Oxide / Rats / Spin Trapping / Thiocarbamates (出版サイトへのリンク) ● Publication site (DOI): 10.1254/jphs.93.417 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14737011 ● Search Scopus @ Elsevier (PMID): 14737011 ● Search Scopus @ Elsevier (DOI): 10.1254/jphs.93.417 (DOI: 10.1254/jphs.93.417, PubMed: 14737011)
97.	Kentaro Kogure, Koichiro Tsuchiya, Kazutoyo Abe, Michinori Akasu, Toshiaki Tamaki, Kenji Fukuzawa and Hiroshi Terada : Direct radical scavenging by the bisbenzylisoquinoline alkaloid cepharanthine., Biochimica et Biophysica Acta (BBA) - General Subjects, Vol.1622, No.1, 1-5, 2003. (要約) Cepharanthine (Ceph) is known as a potent antiperoxidative agent. Recently, we characterized the antiperoxidative effects of Ceph [Biochim. Biophys. Acta 1426 (1999) 133]. However, it was not clear whether the antiperoxidative effect is really due to its direct radical scavenging activity. Therefore, we studied the interaction of Ceph with the hydroxyl radical (OH) by the electron paramagnetic resonance (EPR) technique. Results showed that Ceph actually scavenged OH derived by the Fenton reaction. We also found that Ceph radicals were generated on interaction of Ceph with *OH in neutral aqueous solution, but not in acidic solution, consistent with the pH-dependent anti-lipid peroxidation activity of Ceph. Hence, we concluded that anti-lipid peroxidation by Ceph is due to its direct radical scavenging activity. (キーワード) Alkaloids / Antioxidants / Benzylisoquinolines / Electron Spin Resonance Spectroscopy / Free Radical Scavengers / Hydrogen-Ion Concentration / Hydroxyl Radical / Lipid Peroxidation (出版サイトへのリンク) ● Publication site (DOI): 10.1016/S0304-4165(03)00095-3 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12829254 ● Search Scopus @ Elsevier (PMID): 12829254 ● Search Scopus @ Elsevier (DOI): 10.1016/S0304-4165(03)00095-3 (DOI: 10.1016/S0304-4165(03)00095-3, PubMed: 12829254)
98.	Masanori Yoshizumi, Abe Jun-ichi, Koichiro Tsuchiya, Bradford C.Berk and Toshiaki Tamaki : Stress and vascular responses: Atheroprotective effect of laminar fluid shear stress in endothelial cells: Possible role of mitogen-activated protein kinases ( Review ), Journal of Pharmacological Sciences, Vol.91, No.3, 172-176, 2003. (要約) Atherosclerosis preferentially occurs in areas of turbulent blood flow and low fluid shear stress, whereas laminar blood flow and high shear stress are atheroprotective. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), stimulate expression of endothelial cell (EC) genes that may promote atherosclerosis. Recent findings suggest a steady laminar blood flow decreases EC apoptosis and inhibits TNF-mediated EC activation. EC apoptosis or activation is suggested to be involved in plaque erosion, which may lead to platelet aggregation. TNF-alpha regulates gene expression in ECs, in part, by stimulating mitogen-activated protein (MAP) kinases, which phosphorylate transcription factors. We hypothesized that steady laminar flow inhibits cytokine-mediated activation of MAP kinases in ECs. To test this hypothesis, we determined the effects of steady laminar flow (shear stress = 12 dynes/cm(2)) on TNF-alpha-stimulated activity of three MAP kinases in human umbilical vein ECs (HUVEC): extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. TNF-alpha activated ERK1/2, JNK, and p38 maximally at 15 min in HUVEC. Pre-exposing HUVEC for 10 min to flow inhibited TNF-alpha activation of JNK, but showed no significant effect on ERK1/2 or p38 activation. Incubation of HUVEC with PD98059, a specific ERK1/2 inhibitor, blocked the flow-mediated inhibition of TNF activation of JNK. Transfection studies with dominant-negative constructs of the protein kinase MEK5 suggested an important role for big mitogen-activated protein kinase 1 (BMK1) in flow-mediated regulation of EC activation by TNF-alpha. Understanding the mechanisms by which steady laminar flow regulates JNK activation by cytokines may provide insight into the atheroprotective mechanisms induced by laminar blood flow. (キーワード) Animals / Arteriosclerosis / Blood Vessels / Endothelium, Vascular / Humans / JNK Mitogen-Activated Protein Kinases / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinase 7 / Mitogen-Activated Protein Kinases / Stress, Mechanical / Tumor Necrosis Factor-alpha (出版サイトへのリンク) ● Publication site (DOI): 10.1254/jphs.91.172 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12686737 ● Search Scopus @ Elsevier (PMID): 12686737 ● Search Scopus @ Elsevier (DOI): 10.1254/jphs.91.172 (DOI: 10.1254/jphs.91.172, PubMed: 12686737)
99.	Yuichi Ozawa, Toyoshi Hasegawa, Koichiro Tsuchiya, Masanori Yoshizumi and Toshiaki Tamaki : Effect of endothelin-1(1-31) on the renal resistance vessels., The Journal of Medical Investigation : JMI, Vol.50, No.1-2, 87-94, 2003. (要約) Human chymase produces not only angiotensin II but also endothelin(ET)-1(1-31). We previously reported that ET-1(1-31) had several biological activities in vascular smooth muscle cells. In this study, we investigated the vasoconstrictor effect of ET-1(1-31) on the renal resistance vessels using in vitro microperfused rabbit afferent and efferent arterioles. ET-1(1-31) decreased the lumen diameter of the afferent and efferent arterioles dose-dependently. ET-1(1-31)-induced afferent arteriolar vasoconstriction was not affected by phosphoramidon, an ET converting enzyme inhibitor. ET-1(1-31)-induced renal arteriolar vasoconstriction was inhibited by BQ123, an ETA receptor inhibitor, but not by BQ788, an ETB receptor inhibitor. These results suggest that ET-1(1-31)-induced renal arteriolar vasoconstriction may be mediated by ETA-like receptors. (キーワード) Animals / Arterioles / Aspartic Acid Endopeptidases / Dose-Response Relationship, Drug / Endothelin-1 / Enzyme Inhibitors / Glycopeptides / Humans / Kidney / Male / Metalloendopeptidases / Muscle, Smooth, Vascular / Oligopeptides / Peptide Fragments / Peptides, Cyclic / Perfusion / Piperidines / Rabbits / Receptor, Endothelin A / Receptors, Endothelin / Vascular Resistance / Vasoconstriction / Vasoconstrictor Agents (徳島大学機関リポジトリ) ● Metadata: 110682 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12630573 ● Search Scopus @ Elsevier (PMID): 12630573 (徳島大学機関リポジトリ: 110682, PubMed: 12630573)
100.	Kazuyoshi Kirima, Koichiro Tsuchiya, Hiroyoshi Sei, Toyoshi Hasegawa, Michiyo Shikishima, Yuki Motobayashi, Kyoji Morita, Masanori Yoshizumi and Toshiaki Tamaki : Evaluatin of systemic blood NO dynamics by EPR Spectoscopy: HbNO as an endogenous index of NO, American Journal of Physiology, Heart and Circulatory Physiology, Vol.285, No.2, H589-H596, 2003. (要約) The measurement of hemoglobin-nitric oxide (NO) adduct (HbNO) in whole blood by the electron paramagnetic resonance (EPR) method seems relevant for the assessment of systemic NO levels. However, ceruloplasmin and unknown radical species overlap the same magnetic field as that of HbNO. To reveal the EPR spectrum of HbNO, we then introduced the EPR signal subtraction method, which is based on the computer-assisted subtraction of the digitized EPR spectrum of HbNO-depleted blood from that of sample blood using the software. Rats were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME; 120 mg. kg-1. day-1) for 1 wk to obtain HbNO-depleted blood. When this method was applied to the analysis of untreated fresh whole blood, the five-coordinate state of HbNO was observed. HbNO concentration in pentobarbital-anesthetized rats was augmented (change in [HbNO] = 1.6-5.5 microM) by infusion of L-arginine (0.2-0.6 g/kg) but not D-arginine. Using this method, we attempted to evaluate the effects of temocapril on HbNO dynamics in an L-NAME-induced rat endothelial dysfunction model. The oral administration of L-NAME for 2 wk induced a serious hypertension, and the HbNO concentration was reduced (change in [HbNO] = 5.7 microM). Coadministration of temocapril dose dependently improved both changes in blood pressure and the systemic HbNO concentration. In this study, we succeeded in measuring the blood HbNO level as an index of NO by the EPR HbNO signal subtraction method. We also demonstrated that temocapril improves abnormalities of NO dynamics in L-NAME-induced endothelial dysfunction rats using the EPR HbNO signal subtraction method. (キーワード) Angiotensin-Converting Enzyme Inhibitors / Animals / Arginine / Calibration / Electron Spin Resonance Spectroscopy / Enzyme Inhibitors / Hemoglobins / Hypertension / Male / NG-Nitroarginine Methyl Ester / Nitric Oxide / Rats / Rats, Sprague-Dawley / Thiazepines (出版サイトへのリンク) ● Publication site (DOI): 10.1152/ajpheart.01010.2002 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12663263 ● Search Scopus @ Elsevier (PMID): 12663263 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpheart.01010.2002 (DOI: 10.1152/ajpheart.01010.2002, PubMed: 12663263)
101.	Yuki Suzaki, Masanori Yoshizumi, Yukio Yamashita, Shinji Abe, Koichiro Tsuchiya, Yumiko Satoh, Yasuhiro Kuroda, Kazuya Horike, Masashi Kano, Yoshio Fukuta, Takashi Kitaichi, Takaki Hori, Yutaka Masuda, Tetsuya Kitagawa, Kazuo Minakuchi and Toshiaki Tamaki : Determination of plasma concentrations of endothelin-1(1-31) and endothelin-1 in healthy subjects and patients with atherosclerosis., Journal of Cardiovascular Pharmacology, Vol.41, No.suppl.1, S83-S87, 2003. (要約) We previously found that human chymase cleaves big endothelins at the Tyr31-Gly32 bond and produces 31-amino-acid endothelins, endothelins(1-31). Endothelin-1(1-31) has been isolated from a number of human organs, including the heart and lungs. As endothelin-1 has been shown to play a significant role in the paracrine regulation of cardiovascular functions in humans, it is possible that endothelin-1(1-31) may also exhibit biological activity on human tissues. We previously reported that synthetic endothelin-1(1-31) exhibits a number of physiological actions on cultured cells in vitro. In the present study, we investigated the plasma concentrations of endothelin-1(1-31) and endothelin-1 in healthy subjects and compared them with those in patients with cardiovascular diseases. Endothelin-1(1-31) and endothelin-1 in human plasma was measured using a sandwich-enzyme-immunoassay system, which was recently described for measurement of endothelin-1(1-31). The plasma concentrations of endothelin-1(1-31) and endothelin-1 in healthy volunteers were 19.24 +/- 5.70 and 15.54 +/- 4.45 pg/ml (n = 5), respectively. We also measured plasma concentrations of endothelin-1(1-31) and endothelin-1 before and after surgery in patients with abdominal aortic aneurysms. Before surgery, plasma concentrations of endothelin-1(1-31) and endothelin-1 in these patients were higher than those in healthy individuals. After surgery, both endothelin-1(1-31) and endothelin-1 in plasma decreased to levels similar to those of healthy subjects. This suggests that endothelin-1(1-31) may have similar physiological significance to endothelin-1 in patients with atherosclerosis. (キーワード) Adult / Aged / Aortic Aneurysm, Abdominal / Arteriosclerosis / Endothelin-1 / Humans / Male / Middle Aged / Peptide Fragments (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12688403 ● Search Scopus @ Elsevier (PMID): 12688403 (PubMed: 12688403)
102.	Akiko Kitamura, Shoji Kagami, Maki Urushihara, Syuji Kondo, Masanori Yoshizumi, Toshiaki Tamaki and Yasuhiro Kuroda : Endothelin-1 is a potent stimulator of a1b1 integrin-mediated collagen matrix remodeling by rat mesangial cells., Biochemical and Biophysical Research Communications, Vol.299, No.4, 555-561, 2002. (要約) Endothelin-1 (ET) is known to stimulate mesangial cell (MC) proliferation, extracellular matrix (ECM) synthesis, and thereby contribute to the progression of glomerulonephritis (GN). To clarify the molecular and cellular mechanisms of how ET is involved in the development of glomerular sclerosis, we investigated the influence of ET on the MC-alpha1beta1 integrin-mediated collagen matrix reorganization using a collagen gel contraction assay. ET enhanced MC-alpha1beta1 integrin-mediated gel contraction in a dose-dependent manner. Addition of the endothelin A (ETA) receptor antagonist, BQ123, into collagen gels abolished ET-induced gel contraction by MC. Cell behavior involved in ET-induced gel contraction was investigated in combination with function-blocking anti-alpha1-integrin antibody. Migration and adhesion assays revealed that ET stimulated alpha1beta1 integrin-mediated MC migration but did not influence cell adhesion to type I collagen (collagen I). Integrin-function blocking studies using anti-alpha1 integrin antibody indicated that MC-alpha1beta1 integrin is required not only for collagen-dependent migration, but also for gel contraction. Zymography showed that ET increased MC matrix metalloproteinase-2 (MMP-2) activity in a dose-dependent manner during MC-induced gel contraction process. Finally, flow cytometry analysis indicated that ET did not affect the cell surface expression of the MC-alpha1beta1 integrin within the collagen gel. These data suggested that ET promotes collagen matrix reorganization through the enhancement of MC-alpha1beta1 integrin-dependent migration and MMP-2 activity. We therefore conclude that ET is a potential molecule inducing pathological collagen matrix remodeling observed in progressive GN. (キーワード) Animals / Cell Adhesion / Cell Movement / Cells, Cultured / Collagen / Dose-Response Relationship, Drug / Endothelin-1 / Gels / Glomerular Mesangium / Integrin alpha1beta1 / Matrix Metalloproteinase 2 / Rats / Rats, Sprague-Dawley (出版サイトへのリンク) ● Publication site (DOI): 10.1016/S0006-291X(02)02693-1 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12459174 ● Search Scopus @ Elsevier (PMID): 12459174 ● Search Scopus @ Elsevier (DOI): 10.1016/S0006-291X(02)02693-1 (DOI: 10.1016/S0006-291X(02)02693-1, PubMed: 12459174)
103.	Koichiro Tsuchiya, Kazuyoshi Kirima, Masanori Yoshizumi, Toshiaki Tamaki and Ronald Mason : The role of thiol and nitrosothiol compounds in the NO-forming reactions of the iron-MGD complex., The Biochemical Journal, Vol.367, No.Pt 3, 771-779, 2002. (要約) The object of the present study is to investigate whether the physiologically dominant thiol compounds such as GSH and cysteine or their nitrosothiol compounds affect the formation of the iron- N -methyl-D-glucamine dithiocarbamate [(MGD)(2)Fe(2+)]-nitric oxide complex. The present study provided experimental evidence that physiological concentrations of GSH (approx. 5 mM) and L-cysteine (approx. 0.5 mM) accelerated the formation of the (MGD)(2)Fe(2+)-NO complex from nitrite by two and three times respectively. The rate constants for the reduction of (MGD)(3)Fe(3+) to (MGD)(2)Fe(2+) by GSH and cysteine were calculated as 1.3 and 2.0x10(2) M(-1).s(-1) respectively. Furthermore, depletion of GSH was demonstrated in PC12 cells, and thiol compounds enhanced the formation of reactive oxygen species by the (MGD)(2)Fe(2+) complex by accelerating its redox turnover. The main effect of the physiological concentration of thiols was the reduction of (MGD)(3)Fe(3+). S -nitrosoglutathione spontaneously reacted with (MGD)(2)Fe(2+) to produce the (MGD)(2)Fe(2+)-NO complex with a 1:2 stoichiometry. In fact, (MGD)(2)Fe(2+) was as good an indicator of nitrosothiols as it was of NO itself. The present study elucidates the difficulties of utilizing the (MGD)(2)Fe(2+) complex for the quantification of NO in biological samples, especially in vivo. (キーワード) Animals / Electron Spin Resonance Spectroscopy / Glutathione / Nitric Oxide / Nitroso Compounds / Oxygen / PC12 Cells / Rats / Sorbitol / Spin Labels / Sulfhydryl Compounds / Thiocarbamates (出版サイトへのリンク) ● Publication site (DOI): 10.1042/BJ20020310 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12141947 ● Search Scopus @ Elsevier (PMID): 12141947 ● Search Scopus @ Elsevier (DOI): 10.1042/BJ20020310 (DOI: 10.1042/BJ20020310, PubMed: 12141947)
104.	Masanori Yoshizumi, Toshiaki Kogame, Yuki Suzaki, Yoshiko Fujita, Moe Kyaw, Kazuyoshi Kirima, Keisuke Ishizawa, Koichiro Tsuchiya, Shoji Kagami and Toshiaki Tamaki : Ebselen attenuates oxidative styress-induced apoptosis via the inhibition of the c jun N-terminal kinase and activator protein-1 signaling pathway in PC12 cells., British Journal of Pharmacology, Vol.136, No.7, 1023-1032, 2002. (要約) 1: Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one) is a selenoorganic compound exhibiting both glutathione peroxidase activity and antioxidant activity. Although it has been reported that ebselen is effective for oxidative stress-induced neuronal damage both in vivo and clinically, the precise mechanisms of the efficacy have not yet been elucidated. Thus, we hypothesized that ebselen may affect reactive oxygen species-induced mitogen-activated protein (MAP) kinase activation in cultured PC12 cells. 2: Our findings showed that hydrogen peroxide (H(2)O(2)) stimulated rapid and significant activation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and p38 in PC12 cells, which is a model of catecholamine-containing neurons. 3: H(2)O(2)-induced JNK activation was inhibited by ebselen, whereas ERK1/2 and p38 activation by H(2)O(2) were not affected by ebselen. 4: Inhibition by ebselen of H(2)O(2)-induced hydroxyl radical generation in PC12 cells was observed using electron paramagnetic resonance measurements. Ebselen also inhibited H(2)O(2)-induced increases in DNA binding activity of activator protein-1 (AP-1), a downstream transcription factor of JNK, composed of the c-Jun homo/heterodimer. 5: Finally, pretreatment of cells with ebselen resulted in a significant recovery from cell death including apoptosis by H(2)O(2) in PC12 cells. 6 These findings suggest that ebselen attenuates oxidative stress-induced neuronal cell death through the inhibition of the JNK and AP-1 signalling pathway. Thus, inhibition of JNK by ebselen may imply its usefulness for treatment of ischaemic cerebral diseases relevant to neuronal cell death. (キーワード) Analysis of Variance / Animals / Antioxidants / Apoptosis / Azoles / Cell Survival / DNA Fragmentation / Electron Spin Resonance Spectroscopy / Enzyme Activation / Hydrogen Peroxide / JNK Mitogen-Activated Protein Kinases / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinases / Organoselenium Compounds / Oxidative Stress / PC12 Cells / Rats / Reactive Oxygen Species / Signal Transduction / Time Factors / Transcription Factor AP-1 / p38 Mitogen-Activated Protein Kinases (出版サイトへのリンク) ● Publication site (DOI): 10.1038/sj.bjp.0704808 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12145102 ● Search Scopus @ Elsevier (PMID): 12145102 ● Search Scopus @ Elsevier (DOI): 10.1038/sj.bjp.0704808 (DOI: 10.1038/sj.bjp.0704808, PubMed: 12145102)
105.	Maki Urushihara, Shoji Kagami, Takeshi Kuhara, Toshiaki Tamaki and Yasuhiro Kuroda : Glomerular distribution and gelatinolytic activity of natrix metalloproteinases in human glomerulonephritis., Nephrology, Dialysis, Transplantation, Vol.17, No.7, 1189-1196, 2002. (要約) Matrix metalloproteinases (MMPs) have been implicated in the development of glomerular injury in rat experimental glomerulonephritis (GN). However, the significance of MMPs in human GN remains obscure. In order to evaluate the role of MMPs in human GN, we examined the glomerular distribution and gelatinolytic activities of MMP-2 and MMP-9 in human GN. We performed immunohistochemistry with polyclonal anti-MMP-2 and MMP-9 antibodies, and analysed gelatin zymograms of five isolated glomeruli from various types of human renal disease. The renal specimens investigated were from normal kidneys (n=5), IgA nephritis (n=20), Henoch-Schönlein nephritis (n=4), non-IgA mesangial proliferative GN (n=9), lupus nephritis (n=6), acute poststreptococcal GN (APSGN) (n=4) and diabetic nephropathy (DN) (n=4). MMP-2 immunoreactivity was not detected in normal controls or in any type of GN. MMP-9 staining, which was almost negative in normal glomeruli, was increased mainly in the mesangial region and corresponded to the level of glomerular cell proliferative changes in mesangial proliferative GN (IgA nephritis, Henoch-Schönlein nephritis, non-IgA mesangial proliferative GN and lupus nephritis). Positive but weak staining for MMP-9 was observed in mesangial areas in DN. In addition, double immunostaining showed that MMP-9 is colocalized in scattered neutrophils within diseased glomeruli in APSGN. MMP-9 gelatinolytic activity in five normal glomeruli was weakly detected. Consistent with the levels of immunostaining, MMP-9 glomerular activity was dramatically increased in nephritic glomeruli with IgA nephritis, lupus nephritis and DN. The gelatinolytic activity of MMP-2 was occasionally detectable in nephritic glomeruli. These results strongly suggest that MMP-9 plays an important role in abnormal mesangial proliferative changes in human GN. (キーワード) 細胞分裂 (cell division) / Gelatinases / Glomerulonephritis / Humans / 免疫組織化学 (immunohistochemistry) / Kidney Glomerulus / Matrix Metalloproteinase 2 / Matrix Metalloproteinase 9 / Matrix Metalloproteinases / Reference Values (出版サイトへのリンク) ● Publication site (DOI): 10.1093/ndt/17.7.1189 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12105240 ● Search Scopus @ Elsevier (PMID): 12105240 ● Search Scopus @ Elsevier (DOI): 10.1093/ndt/17.7.1189 (DOI: 10.1093/ndt/17.7.1189, PubMed: 12105240)
106.	Masanori Yoshizumi, Koichiro Tsuchiya, Yuki Suzaki, Kazuyoshi Kirima, Moe Kyaw, Moon Jae-Hak, Junji Terao and Toshiaki Tamaki : Quercetin Glucronide prevents VSMC hypertrophy by angiotensin II via the inhibition of JNK and AP-1 signaling pathway., Biochemical and Biophysical Research Communications, Vol.293, No.5, 1458-1465, 2002. (要約) We previously reported that quercetin, a bioflavonoid belonging to polyphenols, inhibited Angiotensin II (Ang II)-induced vascular smooth muscle cell (VSMC) hypertrophy through the inhibition of c-Jun N-terminal kinase (JNK) activation. However, we recently found that orally administered quercetin appeared in plasma as glucuronide-conjugated forms in rats and humans. Therefore we examined the effect of chemically synthesized quercetin glucuronide on Ang II-induced mitogen-activated protein (MAP) kinase activation and hypertrophy of cultured rat aortic smooth muscle cells (RASMC). Ang II activated extracellular signal-regulated kinase (ERK)1/2, JNK, and p38 in RASMC. Ang II-induced JNK activation was inhibited by quercetin 3-O-beta-d-glucuronide (Q3GA) whereas ERK1/2 and p38 activations were not affected. Q3GA scavenged 1,1-diphenyl-2-picrylhydrazyl radical measured by a method of electron paramagnetic resonance. Q3GA also inhibited Ang II-induced increases in activator protein-1 (AP-1) DNA binding, a downstream transcription factor of JNK. Finally, Ang II-induced [3H]leucine incorporation into RASMC was abolished by Q3GA. These findings suggest that the preventing effect of Q3GA on Ang II-induced VSMC hypertrophy is attributable in part to its inhibitory effect on JNK and the AP-1 signaling pathway. Q3GA would be an active metabolite of quercetin in plasma and may possess a preventing effect for cardiovascular diseases relevant to VSMC growth. (キーワード) Angiotensin II / Animals / Dimerization / Dose-Response Relationship, Drug / Electron Spin Resonance Spectroscopy / Enzyme Activation / Free Radicals / Glucuronides / Humans / JNK Mitogen-Activated Protein Kinases / Leucine / MAP Kinase Signaling System / Male / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinases / Models, Chemical / Muscle, Smooth, Vascular / Protein Binding / Quercetin / Rats / Rats, Sprague-Dawley / Signal Transduction / Time Factors / Transcription Factor AP-1 / p38 Mitogen-Activated Protein Kinases (出版サイトへのリンク) ● Publication site (DOI): 10.1016/S0006-291X(02)00407-2 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12054679 ● Search Scopus @ Elsevier (PMID): 12054679 ● Search Scopus @ Elsevier (DOI): 10.1016/S0006-291X(02)00407-2 (DOI: 10.1016/S0006-291X(02)00407-2, PubMed: 12054679)
107.	Yuki Suzaki, Masanori Yoshizumi, Shoji Kagami, Hajime Koyama, Yutaka Taketani, Hitoshi Houchi, Koichiro Tsuchiya, Eiji Takeda and Toshiaki Tamaki : Hydrogen Peroxide Stimulates c-Src-mediated Big Mitogen-activated Protein Kinase 1(BMK1) and the MEF2C Signaling Pathway in PC12 Cells, The Journal of Biological Chemistry, Vol.277, No.11, 9614-9621, 2002. (要約) Reactive oxygen species, generated by reduction-oxidation (redox) reactions, have been recognized as one of the major mediators of ischemia and reperfusion injury in the brain. Reactive oxygen species-induced cerebral events are attributable, in part, to the change in intracellular signaling molecules including mitogen-activated protein (MAP) kinases. Big MAP kinase 1 (BMK1), also known as ERK5, is a newly identified member of the MAP kinase family and has been reported to be sensitive to oxidative stress. In the present study, we examined the effect of H(2)O(2) on BMK1 activity in PC12 cells, and we investigated the pathophysiological implication of BMK1. Findings showed that BMK1 was rapidly and significantly activated by H(2)O(2) in a concentration-dependent manner in PC12 cells. BMK1 activation by H(2)O(2) was inhibited by both PD98059 and U0126, which were reported to inhibit MEK5 as well as MEK1/2. c-Src was suggested to be involved in BMK1 activation from the experiments with herbimycin A and PP2, specific inhibitors of Src family kinases. Transfection of kinase-inactive Src also inhibited H(2)O(2)-induced BMK1 activation. In addition, H(2)O(2) treatment of cells induced an enhancement of DNA binding activity of MEF2C, a downstream transcription factor of BMK1 in PC12 cells. Finally, pretreatment of cells with PD98059 and U0126 resulted in an increase in cell death including apoptosis by H(2)O(2) in ERK1/2 down-regulated cells as well as in intact PC12 cells. These findings suggest that c-Src mediated BMK1 activation by H(2)O(2) may counteract ischemic cellular damage probably through the activation of MEF2C transcription factor. (キーワード) CENTRAL-NERVOUS-SYSTEM / SMOOTH-MUSCLE CELLS / PROTEIN-KINASE-1 BMK1 / TRANSDUCTION PATHWAY / NEURONAL DIFFERENTIATION / CEREBRAL-ISCHEMIA / TYROSINE KINASES / OXYGEN RADICALS / GENE-EXPRESSION / JUN PROMOTER (出版サイトへのリンク) ● Publication site (DOI): 10.1074/jbc.M111790200 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11782488 ● CiNii @ 国立情報学研究所 (CRID): 1573950401500650880 ● Search Scopus @ Elsevier (PMID): 11782488 ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M111790200 (DOI: 10.1074/jbc.M111790200, PubMed: 11782488, CiNii: 1573950401500650880)
108.	Akiko Kitamura, Shoji Kagami, Maki Urushihara, Syuji Kondo, Masanori Yoshizumi, Toshiaki Tamaki and Yasuhiro Kuroda : Endothelin-1 is a potent stimulator of a1b1 integrin-mediated collagen matrix remodeling by rat mesangial cells., Biochemical and Biophysical Research Communications, Vol.299, 555-561, 2002.
109.	Moe Kyaw, Masanori Yoshizumi, Koichiro Tsuchiya, Kasuyoshi Kirima, Yuki Suzaki, Shinji Abe, Toyoshi Hasegawa and Toshiaki Tamaki : Antioxidants inhibit endothelin-1(1-31)-induced proliferation of vascular smooth muscle cells via the inhibition of mitogen-activated protein (MAP) kinase and activator protein-1 (AP-1)., Biochemical Pharmacology, Vol.64, No.10, 1521-1531, 2002. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/S0006-2952(02)01349-7 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12417265 ● Search Scopus @ Elsevier (PMID): 12417265 ● Search Scopus @ Elsevier (DOI): 10.1016/S0006-2952(02)01349-7 (DOI: 10.1016/S0006-2952(02)01349-7, PubMed: 12417265)
110.	Keisuke Ishizawa, Masanori Yoshizumi, Koichiro Tsuchiya, Eiko Takishita, Yutaka Nakaya, Kazuhiro Kishi, Yousuke Ebina, Hitoshi Houchi, Kazuo Minakuchi and Toshiaki Tamaki : Effects of losartan in combination with or without exercise on insulin resistance in Otsuka Long-Evans Tokushima Fatty rats., European Journal of Pharmacology, Vol.430, No.2-3, 359-367, 2001. (要約) Hypertension often complicates type 2 diabetes mellitus, and angiotensin converting enzyme inhibitor treatment has been shown to improve insulin resistance in such cases. However, the effect of angiotensin II type-1 (AT(1)) receptor antagonists on insulin resistance is still controversial. To gain further information on this effect, we examined the effect of losartan on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Losartan administration alone lowered systolic blood pressure, but did not improve oral glucose tolerance test or insulin resistance in OLETF rats. However, the administration of losartan with exercise significantly improved both systolic blood pressure and insulin resistance relative to control OLETF rats. On the other hand, losartan treatment, regardless of exercise, increased glucose uptake in excised soleus muscle and fat cells. To explore the beneficial effect of losartan on skeletal muscle glucose uptake, we examined intracellular signaling of soleus muscle. Although Akt activity and glucose transporter type 4 (GLUT4) expressions were not affected by losartan with or without exercise, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein (MAP) kinase activities were increased by both interventions. These results indicate that angiotensin AT(1) receptor antagonist improved local insulin resistance, but not systemic insulin resistance. These findings may explain the controversy over the effect of angiotensin AT(1) receptor antagonists on insulin resistance in clinical use. The enhancing effect of angiotensin AT(1) receptor antagonist on skeletal muscle glucose uptake may be attributable to MAP kinase activation or other mechanisms rather than phosphatidylinositol 3-kinase activation. (キーワード) Adipocytes / Animals / Antihypertensive Agents / Blood Glucose / Blood Pressure / Blotting, Western / Body Weight / Deoxyglucose / Diabetes Mellitus, Type 2 / Enzyme Activation / Glucose / Glucose Tolerance Test / Glucose Transporter Type 4 / Heart Rate / Insulin / Insulin Resistance / JNK Mitogen-Activated Protein Kinases / Losartan / Male / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinases / Monosaccharide Transport Proteins / Muscle Proteins / Muscle, Skeletal / Phosphorylation / Physical Conditioning, Animal / Protein-Serine-Threonine Kinases / Proto-Oncogene Proteins / Proto-Oncogene Proteins c-akt / Rats / Rats, Inbred OLETF / p38 Mitogen-Activated Protein Kinases (出版サイトへのリンク) ● Publication site (DOI): 10.1016/S0014-2999(01)01405-4 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11711055 ● Summary page in Scopus @ Elsevier: 2-s2.0-0035798388 (DOI: 10.1016/S0014-2999(01)01405-4, PubMed: 11711055, Elsevier: Scopus)
111.	Masanori Yoshizumi, Koichiro Tsuchiya, Kazuyoshi Kirima, Moe Kyaw, Yuki Suzaki and Toshiaki Tamaki : Quercetin inhibits Shc- and Phosphatidylinositol 3-kinase-mediated c-Jun N-terminal kinase activation by angiotensin II in cultured rat aortic smooth muscle cells., Molecular Pharmacology, Vol.60, No.4, 656-665, 2001. (要約) Angiotensin II (Ang II) induces vascular smooth muscle cell (VSMC) hypertrophy, which results in various cardiovascular diseases. Ang II-induced cellular events have been implicated, in part, in the activation of mitogen-activated protein (MAP) kinases. Although it has been proposed that daily intake of bioflavonoids belonging to polyphenols reduces the incidence of ischemic heart diseases (known as "French paradox"), the precise mechanisms of efficacy have not been elucidated. Thus, we hypothesized that bioflavonoids may affect Ang II-induced MAP kinase activation in cultured rat aortic smooth muscle cells (RASMC). Our findings showed that Ang II stimulated rapid and significant activation of extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38 in RASMC. Ang II-induced JNK activation was inhibited by 3,3',4',5,7-pentahydroxyflavone (quercetin), a major bioflavonoid in foods of plant origin, whereas ERK1/2 and p38 activation by Ang II were not affected by quercetin. Ang II caused a rapid tyrosine phosphorylation of Src homology and collagen (Shc), which was inhibited by quercetin. Quercetin also inhibited Ang II-induced Shc.p85 association and subsequent activation of phosphatidylinositol 3-kinase (PI3-K)/Akt pathway in RASMC. Furthermore, LY294002, a PI3-K inhibitor and a quercetin derivative, inhibited Ang II-induced JNK activation as well as Akt phosphorylation. Finally, Ang II-induced [(3)H]leucine incorporation was abolished by both quercetin and LY294002. These findings suggest that the preventing effect of quercetin on Ang II-induced VSMC hypertrophy are attributable, in part, to its inhibitory effect on Shc- and PI3-K-dependent JNK activation in VSMC. Thus, inhibition of JNK by quercetin may imply its usefulness for the treatment of cardiovascular diseases relevant to VSMC growth. (キーワード) Angiotensin II / Animals / Chromones / Collagen / Dose-Response Relationship, Drug / Drug Interactions / Enzyme Activation / Enzyme Inhibitors / Humans / JNK Mitogen-Activated Protein Kinases / Leucine / Male / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinases / Morpholines / Muscle, Smooth, Vascular / Phosphatidylinositol 3-Kinases / Phosphorylation / Protein-Serine-Threonine Kinases / Proto-Oncogene Proteins / Proto-Oncogene Proteins c-akt / Quercetin / Rats / Rats, Sprague-Dawley / Time Factors / Tritium / Tyrosine / p38 Mitogen-Activated Protein Kinases / src Homology Domains (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11562426 ● Search Scopus @ Elsevier (PMID): 11562426 (PubMed: 11562426)
112.	Shoji Kagami, K Urushihara, K. Loster, W. Reutter, Toshiaki Tamaki, Masanori Yoshizumi and Yasuhiro Kuroda : Requirement for tyrosine kinase-ERK1/2 signaling in a1b1 integrin-mediated collagen matrix remodeling by rat mesangial cells., Experimental Cell Research, Vol.268, No.2, 274-283, 2001. (要約) Abnormal mesangial extracellular matrix remodeling by mesangial cells (MCs) is the hallmark of progressive glomerulonephritis (GN). We recently showed, using a type I collagen gel contraction assay, that alpha 1 beta 1 integrin-dependent MC adhesion and migration are necessary cell behaviors for collagen matrix remodeling. To further determine the mechanism of alpha 1 beta 1 integrin-mediated collagen remodeling, we studied the signaling pathways of MCs that participate in the regulation of collagen gel contraction. Immunoprecipitation and phosphotyrosine detection revealed that gel contraction is associated with the enhanced activity and phosphorylation of ERK1/2 by MCs. The tyrosine kinase inhibitors herbimycin and genistein inhibited collagen gel contraction dose dependently. Furthermore, targeting ERK1/2 activity with a MEK inhibitor, PD98059, and antisense ERK1/2 hindered gel contraction in a dose-dependent manner. Similar inhibitory effects on gel contraction and ERK1/2 phosphorylation were observed when MC-mediated gel contraction was performed in the presence of function-blocking anti-alpha1 or anti-beta1 integrin antibodies. However, cell adhesion and migration assays indicated that PD98059 and antisense ERK1/2 blocked alpha 1 beta 1 integrin-dependent MC migration, but did not interfere with collagen adhesion, although there was a marked decrease in ERK1/2 phosphorylation and ERK1/2 protein expression in cell adhesion on type I collagen. None of the above could affect membrane expression of alpha 1 beta 1 integrin. These results suggested that ERK1/2 activation is critical for the alpha 1 beta 1 integrin-dependent MC migration necessary for collagen matrix reorganization. We therefore conclude that ERK1/2 may serve as a possible target for pharmacological inhibition of pathological collagen matrix formation in GN. (キーワード) Animals / Cell Movement / Collagen / Enzyme Inhibitors / Extracellular Matrix / Flavonoids / Glomerular Mesangium / Integrin alpha1beta1 / Integrins / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinases / Oligodeoxyribonucleotides, Antisense / Phosphorylation / Physical Stimulation / Rats / Rats, Sprague-Dawley / Signal Transduction (出版サイトへのリンク) ● Publication site (DOI): 10.1006/excr.2001.5279 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11478853 ● Summary page in Scopus @ Elsevier: 2-s2.0-0035881282 (DOI: 10.1006/excr.2001.5279, PubMed: 11478853, Elsevier: Scopus)
113.	Ping Cui, Kenji Tani, Hiroko Kitamura, Yuushi Okumura, Mihiro Yano, Daisuke Inui, Toshiaki Tamaki, Saburo Sone and Hiroshi Kido : A novel bioactive 31-amino acid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes, Journal of Leukocyte Biology, Vol.70, No.2, 306-312, 2001. (要約) Endothelin (ET)-1(1-31) is a novel 31-amino acid-length peptide derived from big ET-1 by chymase or other chymotrypsin-type proteases and is a major ET derivative in human neutrophils. In this study, we revealed that ET-1(1-31), but not big ET, exhibited chemotactic activities toward human neutrophils and monocytes as an inflammatory mediator, although the effects were less potent than those of formyl-methionyl-leucyl-phenylalanine or interleukin-8. However, the chemotactic effects of ET-1(1-31) were much greater than those of the 21-amino acid ET-1, ET-1(1-21). Checkerboard analyses revealed that the effects are chemotactic rather than chemokinetic. The effects of ET-1(1-31) are not mediated by interleukin-8 or monocyte chemoattractant protein-1. The chemotactic effects and an increase in intracellular-free Ca(2)(+) caused by ET-1(1-31) were significantly inhibited by BQ123, an ET(A) receptor antagonist, but not by BQ788, an ET(B) receptor antagonist, suggesting that ET-1(1-31) mediates chemotaxis through an ET(A) or ET(A)-like receptor. (キーワード) カルシウム (calcium) / Cells, Cultured / Chemokine CCL2 / Chemotaxis, Leukocyte / Endothelin-1 / Endothelins / Humans / Inflammation Mediators / Interleukin-8 / Kinetics / Monocytes / Neutrophils / Peptide Fragments / Receptors, Endothelin (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11493624 ● Search Scopus @ Elsevier (PMID): 11493624 (PubMed: 11493624)
114.	Kazuyoshi Kirima, Koichiro Tsuchiya, Masanori Yoshizumi, Taisuke Kameda, Hitoshi Houchi, Mami Azuma and Toshiaki Tamaki : Electron paramagnetic resonance study on free radical scavanging and/or generating activity of dopamine-4-0-sulfate., Chemical & Pharmaceutical Bulletin, Vol.49, 576-580, 2001.
115.	Kyaw Moe, Masanori Yoshizumi, Koichiro Tsuchiya, Kazuyoshi Kirima and Toshiaki Tamaki : Antioxidants inhibit JNK and p38 MAPK activation but not ERK 1/2 activation by angiotensin II in rat aortic smooth muscle cells., Hypertension Research, Vol.24, No.3, 251-261, 2001. (要約) Angiotensin II (Ang II) induces vascular smooth muscle cell (VSMC) hypertrophy, which results in several cardiovascular diseases. Ang II-induced cellular events have been mediated, in part, by reactive oxygen species (ROS) which also involve activation of mitogen-activated protein (MAP) kinases. Although it has been proposed that the therapeutic administration of antioxidants is useful for vascular diseases, the precise mechanisms which regulate ROS-sensitive signaling events have not been well characterized. Thus, we hypothesized that antioxidants may affect ROS-mediated MAP kinases activation induced by Ang II. The present findings showed that Ang II stimulated rapid and significant activation of ERK 1/2, JNK and p38 MAPK in cultured rat aortic smooth muscle cells (RASMC). Ang II-induced ERK 1/2 activation was not affected by all antioxidants examined, whereas JNK was sensitive to all antioxidants. In contrast, p38 MAPK activation was inhibited by DPI and ascorbic acid concentration-dependently, but by NAC only at high concentration. DETC and Trolox C had no effects on p38 MAPK activation by Ang II. We further examined the effects of antioxidants on Ang II-induced increases in oxygen consumption as an index of ROS generation in RASMC. DPI strongly inhibited Ang II-induced increases in oxygen consumption. DETC also inhibited Ang II-induced oxygen consumption, whereas ascorbic acid markedly augmented it. These findings suggest that the inhibitory effects of antioxidants on MAP kinases activation in VSMC are attributable, in part, to their modulating effects on ROS generation by Ang II in VSMC. Thus, inhibition of MAP kinases by antioxidants may imply their usefulness for relief of cardiovascular diseases. (キーワード) Acetylcysteine / Angiotensin II / Animals / Antioxidants / Aorta, Thoracic / Ascorbic Acid / Cells, Cultured / Chelating Agents / Chromans / Ditiocarb / Dose-Response Relationship, Drug / Enzyme Inhibitors / Free Radical Scavengers / JNK Mitogen-Activated Protein Kinases / MAP Kinase Kinase 4 / MAP Kinase Signaling System / Male / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinase Kinases / Mitogen-Activated Protein Kinases / Muscle, Smooth, Vascular / Onium Compounds / Oxygen Consumption / Rats / Rats, Sprague-Dawley / Reactive Oxygen Species / Vasoconstrictor Agents / p38 Mitogen-Activated Protein Kinases (出版サイトへのリンク) ● Publication site (DOI): 10.1291/hypres.24.251 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11409648 ● Search Scopus @ Elsevier (PMID): 11409648 ● Search Scopus @ Elsevier (DOI): 10.1291/hypres.24.251 (DOI: 10.1291/hypres.24.251, PubMed: 11409648)
116.	Naoko Okishima, Masanori Yoshizumi, Koichiro Tsuchiya, Ping Cui, Hiroko Kitamura, Toshiaki Tamaki and Hiroshi Kido : Determination of the levels of novel 31-amino acid endothelins and endothelins in human lungs., Life Sciences, Vol.68, No.18, 2073-2080, 2001.
117.	Masanori Yoshizumi, Koichiro Tsuchiya and Toshiaki Tamaki : Signal transduction of reactive oxygen species and mitogen-activated protein kinases in cardiovascular disease, The Journal of Medical Investigation : JMI, Vol.48, No.1,2, 11-24, 2001. (要約) Reactive oxygen species (ROS), generated by reduction-oxidation (redox) reactions, have been recognized as important chemical mediators that regulate signal transduction. It has been reported that increase in ROS generation may relate to a risk for cardiovascular diseases such as atherosclerosis, angina pectoris, and myocardial infarction. Therefore, understanding the ROS-generating biological processes and ROS-induced intracellular signaling will be informative to gain insights into the pathogenesis of these diseases. In this review, we focus on the sources and reactions of ROS in the cardiovascular system and the role of mitogen-activated protein (MAP) kinase pathway in redox-mediated signal transduction. Clinical implications of ROS and MAP kinase are then described to provide insight into the pathogenesis of various redox-sensitive cardiovascular diseases. The pathways responsible for ROS generation in the cardiovascular system may provide novel therapeutic targets. (キーワード) reactive oxygen species / mitogen-activated protein kinase / 情報伝達機構 (signal transduction) / cardiovascular disease (徳島大学機関リポジトリ) ● Metadata: 29055 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11286012 ● Search Scopus @ Elsevier (PMID): 11286012 (徳島大学機関リポジトリ: 29055, PubMed: 11286012)
118.	Daisuke Inui, Masanori Yoshizumi, Yuki Suzaki, Kazuyoshi Kirima, Koichiro Tsuchiya, Hitoshi Houchi, Shoji Kagami and Toshiaki Tamaki : Effect of Endothelin-1(1-31) on p38 Mitogen-Activated Protein Kinase in Cultured Human Mesangial Cells., Life Sciences, Vol.68, No.6, 635-645, 2000. (要約) It was reported that human chymase cleaves big endothelins (ETs) at the Tyr31-Gly32 bond and produces 31-amino acid ETs(1-31). In this study, we investigated the effect of ET-1(1-31) on p38 mitogen-activated protein kinase (p38-MAPK) activity in human mesangial cells (HMCs). By measuring the kinase activity, we demonstrated that ET-1 (1-31) activated the p38-MAPK dose-dependently (10(-9) M to 10(-7) M), which was inhibited by SB203580. The p38-MAPK activation induced by ET-1(1-31) peaked at 10 minutes. BQ123 almost abolished ET-1(1-31)-induced p38-MAPK activation, whereas BQ788 failed to inhibit it. These findings suggest that the stimulatory effect of ET-1(1-31) on p38-MAPK activation is mediated through ET(A) or ET(A)-like receptor. In conclusion, ET-1(1-31) induced increase in p38-MAPK activation in cultured HMCs. (キーワード) Endothelin (出版サイトへのリンク) ● Publication site (DOI): 10.1016/S0024-3205(00)00976-0 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11205878 ● Summary page in Scopus @ Elsevier: 2-s2.0-0034731282 (DOI: 10.1016/S0024-3205(00)00976-0, PubMed: 11205878, Elsevier: Scopus)
119.	Yuichi Ozawa, Hitoshi Houchi, Kazuhiko Teraoka, Mami Azuma, Takehiro Kamimura, Masanori Yoshizumi, Koichiro Tsuchiya, Toshiaki Tamaki and Kazuo Minakuchi : Long-term regulation of catecholamine formation by ouabain in cultured bovine adrenal cromaffin cells., Journal of Cardiovascular Pharmacology, Vol.36, No.suppl.2, S15-S18, 2000. (要約) The long-term effects of ouabain, an inhibitor of Na+/K+ -ATPase, on catecholamine formation in cultured bovine adrenal chromaffin cells were examined. The increase in [14C]catecholamine formation from [14C]tyrosine induced by ouabain was dependent on incubation time, and its maximal effect was observed after incubation for 8 h. The stimulatory effect of ouabain was concentration dependent (10-300 nM), causing maximal stimulation at 300 nM. The formation of [14C]catecholamines induced by ouabain was not increased by incubation with [14C]DOPA instead of [14C]tyrosine. Ouabain-induced [14C]catecholamine formation was influenced by decreases in extracellular Ca2+ concentration, but not by the presence of cycloheximide or actinomycin D. These results suggested that ouabain stimulates continuous activation of hydroxylation of tyrosine through a Ca2+ -dependent mechanism in cultured bovine adrenal chromaffin cells. (キーワード) Animals / Calcium / Catecholamines / Cattle / Cells, Cultured / Chromaffin Cells / Enzyme Inhibitors / Ouabain / Sodium-Potassium-Exchanging ATPase / Tyrosine / Tyrosine 3-Monooxygenase (出版サイトへのリンク) ● Publication site (DOI): 10.1097/00005344-200000006-00005 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11206714 ● Summary page in Scopus @ Elsevier: 2-s2.0-0034480287 (DOI: 10.1097/00005344-200000006-00005, PubMed: 11206714, Elsevier: Scopus)
120.	Masanori Yoshizumi, Shoji Kagami, Yuki Suzaki, Koichiro Tsuchiya, Hitoshi Houchi, Tetsuhiro Hisayama, Hiroyuki Fukui and Toshiaki Tamaki : Effect of endothelin-1(1-31) on human mesangial cell proliferation, The Japanese Journal of Pharmacology, Vol.84, No.2, 146-155, 2000. (キーワード) Endothelin-1(1-31) / Human chymase / Extracellular signal-regulated kinase / Protein kinase C
121.	Ozawa Yuichi, Masanori Yoshizumi, Yasushi Fukuta, Daisuke Inui, Koichiro Tsuchiya, Hitoshi Houchi, Toshiaki Tamaki and Kazuo Minakuchi : Dopamine Clearance During Dopamine Infusion in Infants and Children After Cardiac Surgery, Journal of Cardiovascular Pharmacology, Vol.34, No.Supplement 4, S85-S89, 1999.
122.	Masanori Yoshizumi, Daisuke Inui, Kazuyoshi Kirima, Koichiro Tsuchiya, Hitoshi Houchi, Mami Azuma, Hiroaki Yasuoka, Hiroshi Kido and Toshiaki Tamaki : Comparison of the effects of endothelin-1,-2 and -3(1-31) on changes in [Ca²⁺]i in human coronary artery smooth muscle cells., The Japanese Journal of Pharmacology, Vol.81, 298-304, 1999.
123.	Hiroaki Yasuoka, Masanori Yoshizumi, Daisuke Inui, Naoko Okishima, Hitoshi Houchi, Kazuyoshi Kirima, Shuzo Oshita, Hiroshi Kido and Toshiaki Tamaki : Effect of endothelin-1 (1-31) on intracellular free calcium in cultured human mesangial cells., Life Sciences, Vol.65, No.22, PL267--272, 1999.
124.	Takabumi Umeda, Mami Azuma, Hitoshi Houchi, Toshitaka Ikehara, Fumiaki Shono, Masanori Yoshizumi, Toshiaki Tamaki and Kazuo Minakuchi : Stimulatory effect of enkephalines on calcium efflux from bovine adrenal chromaffin cells in culture., Life Sciences, Vol.65, No.21, PL247-252, 1999.
125.	Daisuke Inui, Masanori Yoshizumi, Okishima Naoko, Hitoshi Houchi, Koichiro Tsuchiya and Toshiaki Tamaki : Mechanism of endothelin-1-(1-31)-induced calcium signaling in human coronary artery smooth muscle cells., American Journal of Physiology, Endocrinology and Metabolism, Vol.276, No.39, E1067-E1072, 1999. (要約) We have found that human chymase produces a 31-amino acid endothelin [ET-1-(1-31)] from the 38-amino acid precursor (Big ET-1). We examined the mechanism of synthetic ET-1-(1-31)-induced intracellular Ca2+ signaling in cultured human coronary artery smooth muscle cells. ET-1-(1-31) increased the intracellular free Ca2+ concentration ([Ca2+]i) in a concentration-dependent manner (10(-14)-10(-10) M). This ET-1-(1-31)-induced [Ca2+]i increase was not affected by phosphoramidon, Bowman-Birk inhibitor, and thiorphan. The ET-1-(1-31)-induced [Ca2+]i increase was not influenced by removal of extracellular Ca2+ but was inhibited by thapsigargin. ET-1-(1-31) at 10(-12) M did not cause Ca2+ influx, whereas 10(-7) M ET-1-(1-31) evoked marked Ca2+ influx, which was inhibited by nifedipine. ET-1-(1-31) also increased inositol trisphosphate formation. These results suggest that the ET-1-(1-31)-induced [Ca2+]i increase at relatively low concentrations is attributable to the release of Ca2+ from inositol trisphosphate-sensitive intracellular stores, whereas Ca2+ influx into the cells evoked by high concentration of ET-1-(1-31) probably occurs through voltage-dependent Ca2+ channels. We concluded that the physiological activity of ET-1-(1-31) may be attributable to Ca2+ mobilization from intracellular stores rather than influx of Ca2+ from extracellular space. (キーワード) endothelin (出版サイトへのリンク) ● Publication site (DOI): 10.1152/ajpendo.1999.276.6.E1067 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10362619 ● Search Scopus @ Elsevier (PMID): 10362619 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpendo.1999.276.6.E1067 (DOI: 10.1152/ajpendo.1999.276.6.E1067, PubMed: 10362619)
126.	Hitoshi Houchi, Mami Azuma, Masanori Yoshizumi, Toshiaki Tamaki and Kazuo Minakuchi : Possible role of bradykinin on stimulus-secretion coupling in adrenal chromaffin cells, The Journal of Medical Investigation : JMI, Vol.46, No.1-2, 1-9, 1999. (要約) Nonapeptide bradykinin is known to be a central nervous system neurotransmitter and to play a role in regulation of neuronal function. However, few details are known of the function of its peptide on stimulus-secretion coupling in neuronal cells. In this article, the role of bradykinin on catecholamine biosynthesis, secretion and Ca2+ movement in adrenal chromaffin cells as a model for catecholamine-containing neurons are examined. Bradykinin receptors are classified as B1 and B2 receptor subtypes. These receptors are present on the adrenal chromaffin cell membrane. Bradykinin increases the influx of Ca2+ and the turnover of phosphoinositide through the stimulation of bradykinin B2 receptor. The secretion of catecholamine from the cells is initiated by the raise of [Ca2+]i. An increase in [Ca2+]i and production of diacylglycerol stimulate the activation of calcium-dependent protein kinases. These kinases stimulate the activation of tyrosine hydroxylase, a rate-limiting enzyme in the biosynthesis of catecholamine. Otherwise, bradykinin increases Ca2+ efflux from the cells through the stimulation of the bradykinin-B2 receptor. This action may be explained by an extracellular Na(+)-dependent mechanism, probably through acceleration of Na+/Ca2+ exchange. It is interesting that bradykinin, which stimulates the biosynthesis and secretion of catecholamine in adrenal chromaffin cells, plays a role in the termination of calcium-signal transduction through the stimulation of Ca2+ efflux from the cells. (キーワード) Bradykinin / Catecholamine / Biosynthesis / Secretion / カルシウム (calcium) (徳島大学機関リポジトリ) ● Metadata: 22088 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10408151 ● Search Scopus @ Elsevier (PMID): 10408151 (徳島大学機関リポジトリ: 22088, PubMed: 10408151)
127.	Koichiro Tsuchiya, Jiang Jin-Jie, Masanori Yoshizumi, Toshiaki Tamaki, Hitoshi Houchi, Kazuo Minakuchi, Kenji Fukuzawa and P.Mason Ronald : Nitric oxide-forming reactions of the water-soluble nitric oxide spin-trapping agent, MGD., Free Rad. Biol. Med., Vol.27, 347-355, 1999.
128.	Yuichi Ozawa, Masanori Yoshizumi, Daisuke Inui, Koichiro Tsuchiya, Hitoshi Houchi, Toshiaki Tamaki and Kazuo Minakuchi : Plasma levels of free and sulfoconjugated catecholamines in patients with atherosclerosis., Biological & Pharmaceutical Bulletin, Vol.22, 657-659, 1999.
129.	Hitoshi Houchi, Masanori Yoshizumi, Koichiro Tsuchiya, Masao Hirose, Tetsuya Kitagawa, Toshihida Kujime, Eiji Shimizu, Yasuharu Niwa, Kazuo Minakuchi and Toshiaki Tamaki : Endothelin-1 stimulates sodium-dependent calcium efflux from bovine adrenal chromaffin cells in culture., British Journal of Pharmacology, Vol.125, No.1, 55-60, 1998.
130.	Masanori Yoshizumi, Tetsuya Kitagawa, Yutaka Masuda, Kazuya Horike, Yoshihiro Ogawa, Y Suzuki, Toshiaki Tamaki and Itsuo Katoh : Effect of Amiloride on Ischaemia and Reperfusion Injury in Isolated,Perfused Rat Hearts, Scandinavian Cardiovascular Journal, Vol.32, No.3, 167-172, 1998. (キーワード) amiloride / Na+/Ca2+ exchange / Na+/H+ exchange / rat heart / reperfusion injury
131.	Masanori Yoshizumi, Tetsuya Kitagawa, Yutaka Masuda, Kazuya Horike, Y Ogawa, Y Suzuki, Toshiaki Tamaki and Itsuo Katoh : Effect of amiloride on ischemia and reperfusion injury in isolated, perfused rat hearts., Scand. Cardiovasc. J., Vol.32, No.3, 167-172, 1998.
132.	Masanori Yoshizumi, Daisuke Inui, Naoko Okishima, Hitoshi Houchi, Koichiro Tsuchiya, Hideki Wakabayashi, Hiroshi Kido and Toshiaki Tamaki : Endothelin-1(1-31), a novel vasoactive peptide, increases [Ca²⁺]i in humen coronary artery smooth muscle cells., European Journal of Pharmacology, Vol.348, No.2-3, 305-309, 1998.
133.	Kenzo Itoh, Masanori Yoshizumi, Tetsuya Kitagawa, Yasushi Fukuta, Takaki Hori, Hitoshi Houchi, Toshiaki Tamaki and Itsuo Katoh : Extracellulary administered lysophosphatidylcholine causes Ca²⁺ efflux from freshly isolated adult rat cardiomyocytes, Basic Research in Cardiology, Vol.93, No.1, 23-29, 1998. (要約) It has previously been reported that ischemia and reperfusion of the heart cause accumulation of lysophosphatidylcholine (LPC) within the myocardium. While it is known that LPC causes the transient increase of intracellular free Ca2+ concentration ([Ca2+]i) during contraction of cardiac cells, little is known about the mechanism for decreasing [Ca2+]i in cardiomyocytes during LPC accumulation. Since cumulative elevation in [Ca2+]i leads to irreversible injury to cardiomyocytes, elevated [Ca2+]i must be restored to an unstimulated level to maintain cell functions. In the present study, we therefore examined the effect of LPC on Ca2+ efflux from freshly isolated adult rat cardiomyocytes. LPC stimulated the efflux of 45Ca2+ from the cells in a concentration-dependent manner (10(-7)M-10(-5)M). Other lysophospholipids, which are generated from phospholipids of the cell membrane, failed to induce 45Ca2+ efflux from the cells. Dilazep and K-7259, which are known to inhibit the increase in [Ca2+]i caused by LPC, likewise reduced 45Ca2+ efflux caused by LPC addition. Furthermore, the LPC-stimulated 45Ca2+ efflux was not affected by removal of extracellular Ca2+, but was dependent on the presence of extracellular Na+. On the other hand, inhibitors of Na+/Ca2+ exchange, amiloride and 5-(N,N-dimethyl)-amiloride, inhibited LPC induced 45Ca2+ efflux. These results suggest that LPC stimulates extracellular Na(+)-dependent 45Ca2+ efflux from freshly isolated adult rat cardiomyocytes, probably through Na+/Ca2+ exchange on the plasma membrane of the cells. (キーワード) Adenosine Triphosphate / Amiloride / Angiotensin II / Animals / Calcium / Cell Membrane / Heart / Lysophosphatidylcholines / Male / Myocardial Contraction / Myocardium / Rats / Rats, Sprague-Dawley / Sodium / Sodium-Calcium Exchanger / Vasoconstrictor Agents (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9538934 ● Search Scopus @ Elsevier (PMID): 9538934 (PubMed: 9538934)
134.	Yasushi Fukuta, Masanori Yoshizumi, Tetsuya Kitagawa, Takaki Hori, Katoh Istuo, Hitoshi Houchi and Toshiaki Tamaki : Effect of Angiotensin II on Ca²⁺ Efflux from Freshly Isolated Adult Rat Cardiomyocytes, --- Possible Involvement of Na⁺/Ca²⁺ Exchanger ---, Biochemical Pharmacology, Vol.55, 481-487, 1998. (キーワード) Angiotensin II / Ca2+ Efflux / Na+/Ca2+ exchanger / losartan / PD123319 / rat / cardiomyocyte
135.	Chen Chunhe, Hitoshi Houchi, Toshiaki Tamaki and Yutaka Nakaya : Effects of cytosolic ATP and other nucleotides on Ca²⁺-activated K⁺ channels in cultures bovine adrenal chromaffin cells., European Journal of Pharmacology, Vol.350, 293-299, 1998.
136.	Toshiataka Ikehara, Park Ho Ki, Hitoshi Houchi, Keiko Hosokawa, Masayuki Shono, Kazuo Minakuchi, Toshiaki Tamaki, Yohsuke Kinouchi, Kazuo Yoshizaki and Hiroshi Miyamoto : Effects of a time-varying strong magnetic field on transient increase in cytosolic free-Ca²⁺ induced by bradykinin in cultured bovine adrenal chromaffin cells., FEBS Letters, Vol.435, 229-232, 1998.
137.	Masanori Yoshizumi, Shokei Kim, Shoji Kagami, Akinori Hamaguchi, Koichiro Tsuchiya, Hitoshi Houchi, Hiroshi Iwao, Hiroshi Kido and Toshiaki Tamaki : Effect of endothelin-1(1-31)on extracellular signal-regulated kinase and proliferation of human coronary artery smooth muscle cells., British Journal of Pharmacology, Vol.125, No.5, 1019-1027, 1998.
138.	Masanori Yoshizumi, Tetsuya Kitagawa, Yuichi Ozawa, Kasutoshi Tano, Koichiro Tsuchiya, Hitoshi Houchi, Kazuo Minakuchi and Toshiaki Tamaki : Changes in plasma free and sulfoconjugated catecholamines during the perioperative period of cardiac surgery:Effect of continuous infusion of dopamine., Biological & Pharmaceutical Bulletin, Vol.21, 787-791, 1998.
139.	Kenzo Ito, Masanori Yoshizumi, Tetsuya Kitagawa, Yasushi Fukuta, Takaki Hori, Hitoshi Houchi, Toshiaki Tamaki and Itsuo Katoh : Extracellulary administered lysophosphatidylcholine causes Ca²⁺ efflux from freshly isolated adult rat cardiomyocytes., Basic Research in Cardiology, Vol.93, 23-29, 1998.
140.	Hiroshi Kido, Ayako Nakano, Naoko Okishima, Hideki Wakabayashi, Fumiko Kishi, Yutaka Nakaya, Masanori Yoshizumi and Toshiaki Tamaki : Human chymase, an enzyme forming novel bioactive 31-amino acid length endothelins., The Journal of Biological Chemistry, Vol.379, 885-891, 1998.
141.	Takaki Hori, Masanori Yoshizumi, Tetsuya Kitagawa, Hitoshi Houchi, Toshiaki Tamaki and Itsuo Katoh : Extracelluar adenosine 5'-triphosphate induces Ca²⁺ effulux from freshly isolated adult rat cardiomyocytes:Possible involvement of Na⁺/Ca²⁺ exchange mechanism., Life Sciences, Vol.61, No.17, 1679-1689, 1997.
142.	Masanori Yoshizumi, Hitoshi Houchi, Yasuo Ishimura, Masao HIrose, Tetsuya Kitagawa, Koichiro Tsustiya, Kazuo Minakuchi and Toshiaki Tamaki : Effect of evodiamine on catecholamine secretion from bovine adrenal medulla., The Journal of Medical Investigation : JMI, Vol.44, No.1,2, 79-82, 1997. (要約) The effect of evodiamine on catecholamine secretion from bovine adrenal medulla was investigated. Evodiamine, a bioactive component isolated from dry unripened fruit of Evodia rutaecarpa Bentham, was found to stimulate the secretion of catecholamine from perfused bovine adrenal medulla at a concentration of 10 microM and its effect persisted for at least 30 min. This stimulatory effect of evodiamine was abolished by omission of Ca2+ from the perfusion fluid. Evodiamine (0.1-10 microM) markedly enhanced the secretion of catecholamine from the adrenal medulla induced by acetylcholine (100 microM or high K+(56 mM). The secretion of catecholamine was promptly enhanced by acetylcholine or high K+, but returned to the control level on treatment for 20 min. However, when evodiamine was added to the perfusion fluid after acetylcholine or high K+ stimulation for 10 min, the secretion of catecholamine again increased greatly. These results indicate that evodiamine not only stimulated the secretion of catecholamine from bovine adrenal medulla but also reversed insensitivity of these cells to acetylcholine or high K+ stimulation. (キーワード) Adrenal Medulla / Animals / Catecholamines / Cattle / Plant Extracts / Quinazolines / Vasodilator Agents (徳島大学機関リポジトリ) ● Metadata: 111645 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9395722 ● Search Scopus @ Elsevier (PMID): 9395722 (徳島大学機関リポジトリ: 111645, PubMed: 9395722)
143.	Hitoshi Houchi, Masanori Yoshizumi, Kazuo Minakuchi, Yasuko Ishimura, Kyoji Morita, Toshiaki Tamaki and Motoo Oka : Potentiation of histamine-induced catecholamine secretion by ouabain in cultured bovine adrenal chromaffin cells is dependent on calcium and sodium influx., Life Sciences, Vol.60, No.23, 2051-2058, 1997.
144.	Kazuo Minakuchi, Hitoshi Houchi, Masanori Yoshizumi, Yasuko Ishimura, Kyoji Morita, Masumitsu Takasugi, Motoo Oka and Toshiaki Tamaki : Serotonin increases Na⁺-dependent Ca²⁺ efflux from bovin sdrenal chromaffin cells in culture., Neuroscience Letters, Vol.223, 17-20, 1997.
145.	Masanori Yoshizumi, Hitoshi Houchi, T Tuchiya, Kazuo Minakuchi, Kazuya Horike, Tetsuya Kitagawa, Itsuo Katoh and Toshiaki Tamaki : Atrial natriuretic peptide stimulates Na⁺-dependent Ca²⁺ effulux from freshly isolated adult rat cardiomyocytes., FEBS Letters, Vol.419, No.2,3, 255-258, 1997.
146.	Kazuya Horike, Masanori Yoshizumi, Tetsuya Kitagawa, Katoh Itoh, Hitoshi Houchi, Toshiaki Tamaki and Itsuo Katoh : Neuropeptide Y as a stimulator of Na⁺-dependent Ca²⁺ effulux from freshly isolated adult rat cardiomyocytes, Naunyn-Schmiedeberg's Arch Pharmacol, Vol.356, No.6, 756-762, 1997.

学術論文(紀要・その他):

1.	冨田修平, 玉置俊晃 : 『低酸素応答転写因子の組織リモデリングへの関与』, 日本薬理学雑誌, Vol.133, No.5, 298, 2009年. (キーワード) Animals / Chronic Disease / Extracellular Matrix / Fibrosis / Humans / Hypoxia-Inducible Factor 1, alpha Subunit / Kidney / Kidney Diseases / Receptors, Oxidized LDL / Signal Transduction (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19554786 ● CiNii @ 国立情報学研究所 (CRID): 1572261550806689536 ● Summary page in Scopus @ Elsevier: 2-s2.0-67649403393 (PubMed: 19554786, CiNii: 1572261550806689536, Elsevier: Scopus)
2.	藤田佳子, 吉栖正典, 井澤有紀, 兼松康久, 玉置俊晃 : ヒト臍帯静脈内皮細胞(HUVEC)における Lysophosphatidylcholine(LPC)刺激によるVEGFレセプターのトランスアクチベーション, 四国医学雑誌, Vol.61, No.3,4, 91-94, 2005年. (要約) One of the major lipid components of oxidized low density lipoprotein, lysophosphatidylcholine(LPC)is involved in numerous biological processes as a bioactive lipid molecule and has beenshown to be involved in the progression of atherosclerosis. As counter-ligands, G2A and GPR4wereidentified with high binding affinity for LPC that are belonging to orphan G-protein-coupledreceptors(GPCRs)at plasma membranes. Although several GPCR ligands transactivate receptortyrosine kinases (RTKs), such as epidermal growth factor receptor, transactivation of RTK byLPC has not yet been reported. Here we observed for the first time that LPC treatment inducestyrosyl phosphorylation of vascular endothelial growth factor(VEGF)receptor2(fetal liverkinase-1/kinase-insert domain-containing receptor, Flk-1/KDR)in human umbilical vein endothelialcells(HUVEC). VEGF receptor tyrosine kinase inhibitors, SU1498and VTKi inhibited Flk-1/KDRtransactivation by LPC. Furthermore, we examined the effect of the Src family kinases inhibitors,Herbimycin A and PP2 on LPC-induced Flk-1/KDR transactivation. Herbimycin A and PP2inhibited Flk-1/KDR transactivation in HUVEC, suggesting that c-Src is involved in LPC-inducedFlk-1/KDR transactivation. Kinase-inactive(KI)Src transfection also inhibited LPC-induced Flk-1/KDR transactivation. In addition, LPC activated extracellular signal-regulated kinase1/2and Akt,which are downstream effectors of Flk-1/KDR, and these were inhibited by SU1498，VTKi,Herbimycin A, PP2and KI Src transfection in HUVEC. LPC-mediated HUVEC proliferation wasshown to be secondary to transactivation because it was suppressed by SU1498，VTKi, HerbimycinA, PP2and KI Src transfection. It is concluded that c-Src-mediated Flk-1/KDR transactivation byLPC may have important implications for the progression of atherosclerosis. (キーワード) LPC / endothelial cells / Flk-1 / KDR / c-Src / 動脈硬化 (atherosclerosis) (徳島大学機関リポジトリ) ● Metadata: 47262 (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1050845762393810304 (徳島大学機関リポジトリ: 47262, CiNii: 1050845762393810304)
3.	兼松康久, 土屋浩一郎, 玉置俊晃 : 生体内における亜硝酸由来のNO産生と，その循環動態への作用検討, 血管, Vol.28, No.2, 39-45, 2005年. (キーワード) 亜硝酸 / NO / EPR / 循環動態 / 虚血 (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1570291225308796032 (CiNii: 1570291225308796032)
4.	吉栖正典, 土屋浩一郎, 兼松康久, 玉置俊晃 : Ⅴ．エンドセリン薬理作用と生理作用心筋障害作用, 日本臨牀, Vol.62, No.9, 622-625, 2004年. (キーワード) エンドセリン / エンドセリン(1ー31) / 心筋障害 / MAP kinase / アポトーシス (apoptosis)
5.	藤守義光, 寺嶋吉保, 玉置俊晃, 森口博基, 相野田紀子, 樫田美雄 : 医療のエスノメソドロジー研究の現状と課題, 徳島大学社会科学研究, Vol.17, No.17, 207-253, 2004年. (徳島大学機関リポジトリ) ● Metadata: 208 (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1520290882837860096 (徳島大学機関リポジトリ: 208, CiNii: 1520290882837860096)
6.	土屋浩一郎, 吉栖正典, 玉置俊晃 : 亜硝酸と一酸化窒素(NO), 血管, Vol.25, No.2, 63-71, 2002年. (キーワード) EPR / 亜硝酸 / NO / ジチオカルバメート錯体 / ニトロチロシン (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1570572700148397056 (CiNii: 1570572700148397056)
7.	吉栖正典, 沖嶋直子, 乾大資, 土屋浩一郎, 玉置俊晃 : エンドセリン1(1-31)の腎作用, 腎と透析, Vol.49, No.4, 739-743, 2000年. (キーワード) エンドセリン
8.	玉置俊晃, 吉栖正典 : 腎微小循環, 日本薬理学雑誌, Vol.113, 261-267, 1999年.
9.	乾大資, 桐間一嘉, 小澤祐一, 須崎友紀, 長谷川豊司, 土屋浩一郎, 吉栖正典, 玉置俊晃 : 単離ウサギ輸入及び輸出細動脈におけるアデノシン受容体, 四国医学雑誌, Vol.55, No.3, 124-130, 1999年. (徳島大学機関リポジトリ) ● Metadata: 112145 (徳島大学機関リポジトリ: 112145)

総説・解説:

1.	堀ノ内裕也, 池田康将, 玉置俊晃 : 肥満・糖尿病とその合併症における生体内鉄蓄積と鉄制限による治療応用への可能性, 日本薬理学雑誌, Vol.154, No.6, 316-321, 2019年12月. (要約) <p>鉄は生体内に最も多く存在する生命機能維持に必須の微量金属元素であり，赤血球のヘモグロビン合成，各種細胞における酸化還元反応，酵素活性，細胞増殖ならびにアポトーシスなどに関与する．そのため，貧血に代表される鉄欠乏疾患はよく知られているものの，鉄過剰疾患はあまり注目されてこなかった．過剰な鉄はフェントン/ハーバー・ワイス反応を介して酸化力が強力なヒドロキシルラジカルを生成し，遺伝性鉄過剰疾患における臓器障害の原因となるが，C型肝炎やアルツハイマー病などの従来は鉄と無関係と考えられていた疾患においても鉄が病態に関与していることが明らかとなり，生体内での鉄の役割が改めて注目されている．近年，生体内鉄量の増加が肥満ならびに糖尿病と関連することが示唆されており，鉄は肥満・糖尿病の増悪因子の可能性がある．しかし，肥満・糖尿病における鉄除去の効果については不明であった．我々は，肥満・糖尿病モデルKKAyマウスを用いて，鉄キレート剤投与が酸化ストレスや炎症を低減して，脂肪細胞肥大の進展が抑制されること，糖尿病性腎臓病モデル<i>db/db</i>マウスでは，食餌性鉄制限が酸化ストレスを減少して，アルブミン尿排泄増加や糸球体病変を抑制することで糖尿病性腎臓病の進行抑制につながることを報告した．本稿では，肥満・糖尿病とその合併症における鉄の役割と鉄制限による治療応用への可能性について，我々が明らかにした研究成果を含めて概説する．</p> (キーワード) 鉄 / 酸化ストレス / 肥満 / 糖尿病 (出版サイトへのリンク) ● Publication site (DOI): 10.1254/fpj.154.316 (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1390001277399772544 ● Search Scopus @ Elsevier (DOI): 10.1254/fpj.154.316 (DOI: 10.1254/fpj.154.316, CiNii: 1390001277399772544)
2.	今西正樹, 石澤啓介, 櫻田巧, 石澤有紀, 山野範子, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : 酸化ストレス制御を基盤とする新規心腎血管障害治療薬の開発, 薬学雑誌, Vol.134, No.6, 715-719, 2014年6月. (要約) Oxidative stress is a key factor involved in the pathogenesis and progression of cardiovascular disease (CVD) and chronic kidney disease (CKD). Reactive oxygen species (ROS), produced as a result of redox reactions in various cells, have been recognized as key chemical mediators causing cellular damage and organ dysfunction in CVD and CKD. Nifedipine, a well-known calcium channel blocker, is extremely sensitive to light which gets converted to its nitroso analog, nitrosonifedipine (NO-NIF) in the presence of ultraviolet and visible light. The so formed NO-NIF blocks calcium channel quite weakly compared to that of nifedipine. However, we elucidated for the first time that NO-NIF is converted to NO-NIF radical which acquires extremely strong antioxidant property via reaction with unsaturated fatty acid or endothelial cells. We have already reported that NO-NIF reduces the cytotoxicity of cumene hydroperoxide, which hampers the integrity of cell membrane through oxidative stress, in endothelial cells. Additionally, we demonstrated that NO-NIF restored acetylcholine-responsive vascular relaxation and suppressed intercellular adhesion molecule-1 expression in the aorta of N(ω)-nitro-L-arginine methyl ester-treated rats, a model of vascular endothelial dysfunction. Recently, we reported that NO-NIF ameliorates angiotensin II-induced vascular remodeling via antioxidative effects in vivo and in vitro. These observations point towards the plausible, unique role of NO-NIF as a novel antioxidant which improves vascular dysfunction for overcoming CVD and CKD and the same has been highlighted in this review. (キーワード) 酸化ストレス (oxidative stress) / chronic kidney disease / cardiovascular disease / nitrosonifedipine (出版サイトへのリンク) ● Publication site (DOI): 10.1248/yakushi.13-00255-4 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24882646 ● Search Scopus @ Elsevier (PMID): 24882646 ● Search Scopus @ Elsevier (DOI): 10.1248/yakushi.13-00255-4 (DOI: 10.1248/yakushi.13-00255-4, PubMed: 24882646)
3.	池田康将, 土屋浩一郎, 玉置俊晃 : 抗酸化薬, 腎・高血圧の最新治療, Vol.3, No.2, 93-99, 2014年4月.
4.	池田康将, 土屋浩一郎, 玉置俊晃 : 糖尿病と食事由来金属元素, 糖尿病, Vol.56, No.12, 919-921, 2013年12月. (キーワード) 金属元素 / 糖尿病 / 酸化ストレス (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1520290882774966784 ● Summary page in Scopus @ Elsevier: 2-s2.0-84892762387 (CiNii: 1520290882774966784, Elsevier: Scopus)
5.	冨田修平, 木平孝高, 玉置俊晃 : 血管リモデリングにおけるT細胞の低酸素応答性転写因子の役割, 生化学, Vol.85, No.4, 265-268, 2013年4月. (キーワード) Animals / Anoxia / Blood Vessels / Disease Models, Animal / Humans / Hypoxia-Inducible Factor 1 / Mice / Mice, Knockout / T-Lymphocytes (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23717872 ● CiNii @ 国立情報学研究所 (CRID): 1520853832244865152 ● Search Scopus @ Elsevier (PMID): 23717872 (PubMed: 23717872, CiNii: 1520853832244865152)
6.	櫻田巧, 石澤啓介, 今西正樹, 藤井聖子, 谷口順平, 石澤有紀, 宮本理人, 木平孝高, 池田康将, 冨田修平, 水口和生, 土屋浩一郎, 玉置俊晃 : Nitrosonifedipineはangiotensin IIによるマウス血管リモデリングを抑制する, 腎とフリーラジカル, Vol.11, 78-81, 2013年1月.
7.	池田康将, 田島壮一郎, 土屋浩一郎, 玉置俊晃 : Iron metabolism in the progression of adipocyte hypertrophy, 細胞, Vol.44, No.6, 282-286, 2012年6月.
8.	池田康将, 田島壮一郎, 山野範子, 土屋浩一郎, 玉置俊晃 : 循環器疾患と糖尿病における生体内鉄の意義, 血管, Vol.34, No.2, 75-85, 2011年7月. (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1572543024868677632 (CiNii: 1572543024868677632)
9.	冨田修平, 今西正樹, 櫻田巧, 山野範子, 木平孝高, 池田康将, 玉置俊晃 : 生体の低酸素応答と病態 -血管リモデリングにおける転写因子HIFの関与-, 四国医学雑誌, Vol.67, No.1, 2, 3-6, 2011年4月. (要約) Recent studies have shown that the cellular immune response to the hypoxic microenvironment constructed by vascular remodeling development modulates the resulting pathologic alterations. A major mechanism mediating adaptive responses to reduced oxygen availability is the regulation of transcription by hypoxia-inducible factor1(HIF‐1). Impairment of HIF‐1‐ dependent inflammatory responses in T cells causes an augmented vascular remodeling induced by arterial injury, which is shown as prominent neointimal hyperplasia and increase in infiltration of inflammatory cells at the adventitia in mice lacking Hif‐1α specifically in T cells. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice have shown enhanced production of cytokines in activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. This minireview shows that HIF‐1α in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of the T cell-mediated immune response and suggests potential new therapeutic strategies that target HIF‐1α. (キーワード) vascular remodeling / hypoxia / hypoxia-inducible factor (徳島大学機関リポジトリ) ● Metadata: 110344 (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1050564287418524160 (徳島大学機関リポジトリ: 110344, CiNii: 1050564287418524160)
10.	石澤啓介, 水口和生, 玉置俊晃 : 医療人としての薬剤師育成教育の実践, --- ∼米国の薬学教育ならび日本の医学教育から学ぶ∼ ---, 医薬ジャーナル, Vol.43, No.3, 871-874, 2007年3月.
11.	玉置俊晃, 山口邦久, 石澤啓介 : 薬理作用から見た健康食品, 四国医学雑誌, Vol.63, No.5,6, 170-171, 2007年. (徳島大学機関リポジトリ) ● Metadata: 110195 (徳島大学機関リポジトリ: 110195)
12.	吉栖正典, 石澤啓介, 井澤有紀, 玉置俊晃 : インスリン抵抗性による血管障害の細胞内情報伝達機構, 日本薬理学雑誌, Vol.128, No.3, 147-151, 2006年9月. (要約) 近年，メタボリック症候群の疾患概念が確立され，本邦でもその診断基準が発表された．メタボリック症候群の根底にはインスリン抵抗性が存在するといわれるが，高血圧，動脈硬化などの血管病にインスリン抵抗性がどのように関っているかは未だ明らかではない．我々はこの数年，血管病の発症，進展に関わるインスリン抵抗性の細胞内情報伝達機構について研究を行なってきた．糖尿病モデル動物のOLETFラットを用いた検討では，アンジオテンシンII受容体拮抗薬の投与が末梢での糖利用臓器のインスリン抵抗性を改善させ，レニン-アンジオテンシン系のメタボリック症候群への関与が示唆された．培養血管平滑筋細胞を用いた細胞内情報伝達機構の検討では，アンジオテンシンII刺激によって活性化されるMAPキナーゼの一つ，ERK1/2がインスリン抵抗性の発現に関与していることが明らかになった．また，血管リモデリング進展過程のひとつである血管平滑筋細胞の遊走において，SrcチロシンキナーゼやCasアダプタータンパクが細胞内分子として重要な役割を果たしていることを見いだした．血管病におけるインスリン抵抗性に関わる標的分子の探求は，今後も増加することが予想されるメタボリックシンドローム治療のための創薬に有用な情報をもたらすことが期待される．<br> (キーワード) メタボリックシンドローム / インスリン抵抗性 / アンジオテンシンII / MAPキナーゼ / 血管平滑筋細胞 (出版サイトへのリンク) ● Publication site (DOI): 10.1254/fpj.128.147 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16971777 ● CiNii @ 国立情報学研究所 (CRID): 1390001204271623040 ● Search Scopus @ Elsevier (PMID): 16971777 ● Search Scopus @ Elsevier (DOI): 10.1254/fpj.128.147 (DOI: 10.1254/fpj.128.147, PubMed: 16971777, CiNii: 1390001204271623040)

国際会議:

1.	Yuya Horinouchi, Yasumasa Ikeda, Keijo Fukushima, Masaki Imanishi, Yuki Izawa-Ishizawa, Yoshito Zamami, Hiromichi Fujino, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Utilizing Real-World Big Data in the Search for New Renoprotective Drugs, Joint Hypertension 2018 Scientific Sessions, Sep. 2018.
2.	Yuya Horinouchi, Yasumasa Ikeda, Keijo Fukushima, Masaki Imanishi, Yuki Izawa-Ishizawa, Yoshito Zamami, Hiromichi Fujino, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Renoprotective effects of edoxaban, a factor Xa inhibitor, 18th World Congress of Basic and Clinical Pharmacology, Jul. 2018.
3.	Yuki Izawa-Ishizawa, Masaki Imanishi, kotoko suzuki, Yuya Horinouchi, Kenshi Takechi, Yoshito Zamami, Koichiro Tsuchiya, Toshiaki Tamaki, Keisuke Ishizawa and Yasumasa Ikeda : The effect of quercetin on aortic aneurysms in mice, WCP2018, Jul. 2018.
4.	濱野裕章, Yasumasa Ikeda, Yuya Horinouchi, Yoshito Zamami, Masaki Imanishi, Yuki Izawa-Ishizawa, Licht Miyamoto, Koichiro Tsuchiya, Keisuke Ishizawa and Toshiaki Tamaki : Proton Pump Inhibitor Involves Abnormality of Iron Metabolism through Hepcidin Regulation, 18th World Congress of Basic and Clinical Pharmacology, Jul. 2018.
5.	Yoshito Zamami, Yuki Izawa-Ishizawa, Kenshi Takechi, Masaki Imanishi, Keijo Fukushima, Yuya Horinouchi, Yasumasa Ikeda, Hiromichi Fujino, Toshiaki Tamaki and Keisuke Ishizawa : Search for drugs that attenuate the anti tumor effect of bevacizumab using adverse event database, 18th World Congress of Basic and Clinical Pharmacology, Jul. 2018.
6.	Licht Miyamoto, Aihara Haruna, Xu Wenting, Jin Meina, Tomida Yosuke, Yamaoka Tomomi, Tanaka Naonobu, Ikeda Yasumasa, Toshiaki Tamaki, Yoshiki Kashiwada and Koichiro Tsuchiya : A limonene-derivative purified from peels of Citrus Sudachi ameliorates lipid and glucose metabolism through upregulating sirt1, World Congress of Pharmacology, Kyoto, Jul. 2018.
7.	Yuya Horinouchi, Yasumasa Ikeda, Hirofumi Hamano, Masaki Imanishi, Yuki Izawa-Ishizawa, Yoshito Zamami, Kenshi Takechi, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : The effect of iron on skeletal muscle atrophy in chronic kidney disease., Free Radical Biology and Medicine, Vol.112, No.1, 204-205, Dec. 2017. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.freeradbiomed.2017.10.323 (文献検索サイトへのリンク) ● Search Scopus @ Elsevier (DOI): 10.1016/j.freeradbiomed.2017.10.323 (DOI: 10.1016/j.freeradbiomed.2017.10.323)
8.	hirofumi Hamano, Yasumasa Ikeda, Hiroaki Watanabe, Yuya Horinouchi, Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Indoxyl Sulfate Disturbs Normal Iron Metabolism via Hepcidin Upregulation in Chronic Kidney Disease, ASN Kidney Week 2017 Annual Meeting, Nov. 2017.
9.	Yuya Horinouchi, Yasumasa Ikeda, Masaki Imanishi, Yoshito Zamami, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Direct activated factor X inhibitor attenuates renal fibrosis on unilateral ureteral obstruction-induced nephrotoxicity., 53rd Congress of the European Societies of Toxicology (eurotox2017), Sep. 2017.
10.	Yuya Horinouchi, Yasumasa Ikeda, Masaki Imanishi, Yoshito Zamami, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : FACTOR XA INHIBITOR ATTENUATES RENAL INTERSTITIAL FIBROSIS IN MICE WITH UNILATERAL URETERAL OBSTRUCTION, THE 13TH CONGRESS OF THE EUROPEAN ASSOCIATION FOR CLINICAL PHARMACOLOGY AND THERAPEUTICS(EACPT2017), Jun. 2017.
11.	Yuki Izawa-Ishizawa, Keisuke Ishizawa, 田淵正樹, Masaki Imanishi, Mai Takata, Eriko Sairyo, Yoshito Zamami, Yuya Horinouchi, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : NITROSONIFEDIPINE, A NOVEL ANTIOXIDANT, AMELIORATES NEUROLOGICALSYMPTOMS AND PROLONGS THE SURVIVAL IN A MALIGNANT STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS, 27th European Meeting on Hypertension and Cardiovascular Protection, Jun. 2017.
12.	Masaki Imanishi, Kyohei Tanaka, Raiki Ikutoh, Yoshito Zamami, Kenshi Takechi, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yasumasa Ikeda, Hiromichi Fujino, Koichiro Tsuchiya, Toshiaki Tamaki and Keisuke Ishizawa : THE EFFECTS OF FEBUXOSTAT ON ANGIOTENSIN II-INDUCED VASCULAR REMODELING, 27th European Meeting on Hypertension and Cardiovascular Protection, Jun. 2017.
13.	Yasumasa Ikeda, Yuya Horinouchi, Yuki Izawa-Ishizawa and Toshiaki Tamaki : IRON RESTRICTION PREVENTS RENAL TUBULOINTERSTITIAL INJURY INDUCED BY ALBUMIN OVERLOAD IN MICE, 54th ERA-EDTA Congress, Madrid, Jun. 2017.
14.	Yasumasa Ikeda, Yuya Horinouchi, Yuki Izawa-Ishizawa and Toshiaki Tamaki : DIRECT FACTOR XA INHIBITOR PREVENTS RENAL INTERSTITIAL FIBROSIS IN MICE WITH UNILATERAL URETERAL OBSTRUCTION, 54th ERA-EDTA Congress, Madrid, Jun. 2017.
15.	Licht Miyamoto, Fukuta Keisuke, Takahashi Rie, Umemoto Kana, Okuno Hiroko, Yasumasa Ikeda, Toshiaki Tamaki and Koichiro Tsuchiya : Fragrance of aromatic oil from peels of Citrus sudachi causes adipose browning and ameliorates glucose and lipid metabolism, EMBO workshop, Sitges, Spain, May 2017.
16.	Hirofumi Hamano, Yasumasa Ikeda, Hiroaki Watanabe, Yuya Horinouchi, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Indoxyl Sulfate Involves Abnormality of Iron Metabolism through Hepcidin Regulation, Experimental Bioogy 2017, Chicago, Apr. 2017.
17.	Koichiro Tsuchiya, Aihara Haruna, Xu Wenting, Jin Meina, Tomida Yosuke, Yamaoka Tomomi, Naonobu Tanaka, Yasumasa Ikeda, Akira Shigenaga, Akira Otaka, Toshiaki Tamaki, Yoshiki Kashiwada and Koichiro Tsuchiya : A limonene-derivative from Sudachi peel activates sirt1 and improves lipid and glucose metabolism in high fat diet-fed mice., 欧州糖尿病学会, Dec. 2016.
18.	Ota Kazuma, Yoshitaka Kihira, Kishibuchi Reina, Yuki Izawa-Ishizawa, Yuya Horinouchi, Yasumasa Ikeda and Toshiaki Tamaki : Disruption of hypoxia-inducible factor-1a deteriorates renal ischemia-reperfusion injury through dysregulation of Kv2.2-induced apoptosis in tubules., ASN KIDNEY WEEK 2016, Chicago, Nov. 2016.
19.	Maki Urushihara, T Nagai, Shuji Kondo, Toshiaki Tamaki, Yasumasa Ikeda and Shoji Kagami : (Pro)renin receptor-mediated ERK1/2 and Wnt signaling pathway in crescent glomerulonephritis., Kidney Week 2016, Nov. 2016.
20.	Yoshito Zamami, Mitsui Marin, Moriguchi Hiroshi, Kenshi Takechi, Masaki Imanishi, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya, Kawasaki Hiromu, Toshiaki Tamaki and Keisuke Ishizawa : Search for a preventative therapy for Bevacizumab-induced hypertension using the drug repositioning approach, 7th Scientific Meeting of Asian Society for Vascular Biology, Oct. 2016.
21.	Fukuta Keisuke, Licht Miyamoto, Takahashi Rie, Toshiaki Tamaki, Ikeda Yasumasa and Tsuchiya Koichiro : Eessential oil from sudachi peal improves glucose and lipid metabolism, 11th IDF-WPR Congress 2016 & 8th AASD Scientific Meeting (Taipei, Taiwan), Oct. 2016.
22.	Yutaka Fukunaga, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki and Ichiro Hashimoto : Topical Application of Nitrosonifedipine, a Novel Free Radical Scavenger, Ameliorate the Ischemic Skin Flap Necrosis, Plastic Surgery THE MEETING 2016, Los Angeles, Sep. 2016.
23.	Yuki Izawa-Ishizawa, Masaki Imanishi, Yuya Horinouchi, Kenshi Takechi, Yoshito Zamami, Yasumasa Ikeda, Koichiro Tsuchiya, Toshiaki Tamaki and Keisuke Ishizawa : The effects of pitavastatin, a lipid-lowering agent, against aortic dissection model mice induced by L-NAME, a nitric oxide synthase inhibitor., The 9th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide/16th Annual Scientific Meeting of the Nitric Oxide Society of Japan., May 2016.
24.	Yasumasa Ikeda, Yuya Horinouchi, Yuki Izawa-Ishizawa and Toshiaki Tamaki : The new insight of iron on tissue damage in metabolic disorders., The 9th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide/16th Annual Scientific Meeting of the Nitric Oxide Society of Japan., May 2016.
25.	Koichiro Tsuchiya, Licht Miyamoto, Tomida Yosuke, Yamane Megumi, Tsuda Katsunori, Yasumasa Ikeda and Toshiaki Tamaki : Dietary nitrite ameliorates glucose tolerance and hyperlipidemia in diet-induced obesity rats., The 16th Annual Scientific Meeting of the Nitric Oxide Society of Japan / The 9th Internatinal Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide. (Seindai, Japan) 2016.5, May 2016.
26.	Yasumasa Ikeda, Keisuke Oshima, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : The Involvement of Iron Supplementation on Erythropoietin Expression, Experimental Biology 2016, Apr. 2016.
27.	宮本理人, 粟飯原遥奈, 許文てい, ジン美娜, 冨田洋介, 山岡朋美, 田中直伸, 池田康将, 玉置俊晃, 柏田良樹, 土屋浩一郎 : スダチ果皮からの抗メタボリックシンドローム活性を有する物質の同定, 糖尿病, No.59, 京都, 2016年.
28.	FUKUTA Keisuke, Licht Miyamoto, TAKAHASHI Rie, Toshiaki Tamaki, Yasumasa Ikeda and Koichiro Tsuchiya : 11th IDF-WPR Congress 2016 & 8th AASD Scientific MeetingPosterEessentialoil fromsudachipealimprovesglucoseandlipidmetabolism, 2016.
29.	Licht Miyamoto, Yuki Tsuchihashi, Yosuke Tomida, Megumi Yamane, Kazuya Takenokuma, Yasumasa Ikeda, Toshiaki Tamaki and Koichiro Tsuchiya : Dietary nitrite ameliorates glucose tolerance and hyperlipidemia in diet-induced obese rats, The 6th International Conference on Food Factors, Seoul, Nov. 2015.
30.	Yasumasa Ikeda, Hamano Hirofumi, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Bilirubin Enhances Ischimia-induced Angiogenesis Through Akt-eNOS-Dependent Signaling Pathway, American Heart Association Scientific Sessions 2015, Orlando, Nov. 2015.
31.	Wenting Xu, Licht Miyamoto, Haruna Aihara, Tomomi Yamaoka, Keisuke Ishizawa, Toshiaki Tamaki, Yoshiki Kashiwada and Koichiro Tsuchiya : The Mechanism of Citrus sudachi Peel Extract Exerts Lipid Reducing Effect in Cells, 2015.10.19-22 The 10th IAGG Asia / Oceania Congress of Gerontology and Geriatrics 2015, Chiang Mai, Oct. 2015.
32.	宮本理人, 粟飯原遥奈, Wenting Xu, Meina Jin, 冨田洋介, 山岡朋美, 田中直伸, 池田康将, 重永章, 大髙章, 玉置俊晃, 柏田良樹, 土屋浩一郎 : リモネン誘導体によるsirt1活性化を介した脂質低下作用, 日本肥満学会，アジアオセアニア糖尿病学会, 名古屋, 2015年10月.
33.	Licht Miyamoto, Haruna Aihara, Wenting Xu, Meina Jin, Yosuke Tomida, Tomomi Yamaoka, Naonobu Tanaka, Yasumasa Ikeda, Akira Shigenaga, Akira Otaka, Toshiaki Tamaki, Yoshiki Kashiwada and Koichiro Tsuchiya : Limonene-derivative Ameliorates Lipid Profiles by Upregulation of Sirt1 Activity and Expression in Cultured Cells and High Fat Diet-Fed Mice, American diabetes association, Boston, Jun. 2015.
34.	Yuki Izawa-Ishizawa, Keisuke Ishizawa, Toya Hiroki, Yoshitaka Kihira, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : Novel aortic dissection model by pharmacologically-induced endothelial dysfunction, 17th International Congress on Atherosclerosis 2015, Amsterdam, May 2015.
35.	Yasumasa Ikeda, Yusuke Kanai, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : The Effects of Bilirubin on Angiogenesis in Mice with Hindlimb Ischemia, Experimental Biology 2015, Boston, Mar. 2015.
36.	今西正樹, 井口道代, 冨田紀子, Tsounapi Panagiota, 松永慎司, 玉置俊晃, 冨田修平 : 平滑筋由来HIF-1αは薬剤誘導性大動脈瘤形成に対して保護的に作用する, 第1回国際心血管薬物療法学会日本部会, 2015年.
37.	Yuya Horinouchi, A Fiona Summers, Marilyn Ehrenshaft, Kazuyoshi Kawazoe, Koichiro Tsuchiya, Toshiaki Tamaki and P Ronald Mason : Investigating free radical generation in HepG2 cells using immuno-spin trapping., Free Radical Biology and Medicine, Vol.75 Suppl 1, Dec. 2014. (要約) Oxidative stress can induce the generation of free radicals, which are believed to play an important role in both physiological and pathological processes and a number of diseases such as cancer. Therefore, it is important to identify chemicals which are capable of inducing oxidative stress. In this study, we evaluated the ability of four environmental chemicals, aniline, nitrosobenzene (NB), N,N-dimethylaniline (DMA) and N,N-dimethyl-4-nitrosoaniline (DMNA), to induce free radicals and cellular damage in the hepatoma cell line HepG2. Cytotoxicity was assessed using lactate dehydrogenase (LDH) assays and morphological changes were observed using phase contrast microscopy. Free radicals were detected by immuno-spin trapping (IST) in in-cell western experiments or in confocal microscopy experiments to determine the subcellular localization of free radical generation. DMNA induced free radical generation, LDH release and morphological changes in HepG2 cells whereas aniline, NB and DMA did not. Confocal microscopy showed that DMNA induced free radical generation mainly in the cytosol. Preincubation of HepG2 cells with N-acetylcysteine and 2,2'-dipyridyl significantly prevented free radical generation upon subsequent incubation with DMNA, whereas preincubation with apocynin and dimethyl sulfoxide did not. These results suggest that DMNA induces oxidative stress and that reactive oxygen species, metals and free radical generation play a critical role in DMNA-induced cytotoxicity. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.freeradbiomed.2014.10.768 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26461344 ● Search Scopus @ Elsevier (PMID): 26461344 ● Search Scopus @ Elsevier (DOI): 10.1016/j.freeradbiomed.2014.10.768 (DOI: 10.1016/j.freeradbiomed.2014.10.768, PubMed: 26461344)
38.	Jamba Ariunbold, Shuji Kondo, Nagai Takashi, Maki Urushihara, Toshiaki Tamaki and Shoji Kagami : Hic-5 Regulates Mesangial Cell Proliferation via Altered and Coordinated Expression of Cell Cycle-Related Protein, American Society of Nephrology (ASN) Kidney Week 2014, Philadelphia, Nov. 2014.
39.	Maki Urushihara, Shuji Kondo, Kobori Hiroyuki, Toshiaki Tamaki and Shoji Kagami : Urinary angiotensinogen as a specific biomarker of intrarenal renin-angiotensin system status associated with glomerular injury in pediatric IgA nephropathy patients, American Society of Nephrology (ASN) Kidney Week 2014, Philadelphia, Nov. 2014.
40.	Keisuke Ishizawa, Kohara Yusuke, Sakurada Takumi, Toya Hiroki, Iki Yutaka, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : Nitrosonifedipine ameliorates the progression of aortic aneurysms by exerting antioxidative effects, ESC Congress 2014, Barcelona, Sep. 2014.
41.	Yasumasa Ikeda, Soichiro Tajima, Mizuki Imao, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Ferritin induces IL-1 production through inflammasome activation via NF-B-dependent manner in macrophages, Experimental Biology 2014, San Diego, Apr. 2014.
42.	Licht Miyamoto, Yamane Megumi, Tomida Yosuke, Takenokuma Kazuya, Keisuke Ishizawa, Toshiaki Tamaki and Koichiro Tsuchiya : Significance of AMPK in renal protective and metabolic actions of nitrite, international conference of food science, Kyoto, Mar. 2014.
43.	Licht Miyamoto, Tomida Y, Takenokuma K, Yamane M, Keisuke Ishizawa, Toshiaki Tamaki and Koichiro Tsuchiya : Dietary nitrite ameliorates glucose and lipid metabolism in high fat diet-fed rats., 2014 Keystone Symposia Conference, Jan. 2014.
44.	Taisuke Nakayama, Hirotsugu Kurobe, Noriko Sugasawa, Hajime Kinoshita, Yasushi Yoshida, Yoichiro Hirata, Mie Sakata, Mark Webster Maxfield, Michio Shimabukuro, Yousuke Takahama, Masataka Sata, Toshiaki Tamaki, Tetsuya Kitagawa and Shuhei Tomita : Macrophage-Specific Hypoxia-Inducible Factor (HIF)-1-Deficient Mice Suppress the Vascular Remodeling and Regulate M2 Macrophage Polarization, American Heart Association AHA 2013, Nov. 2013.
45.	S Jamba, Shuji Kondo, Maki Urushihara, T Nagai, Toshiaki Tamaki and Shoji Kagami : Contribution of hydrogen peroxide-inducible clone-5 to the regulation of mesangial cell proliferation in mesangioproliferative glomerulonephritis, The annual meeting of American society of nephrology Kidney Week 2013, Nov. 2013.
46.	Keisuke Ishizawa, Noriko Yamano, Hiroyuki Kobori, Maki Urushihara, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : Nitrosonifedipine prevents the progression of diabetic nephropathy via attenuating the expression of intrarenal angiotensinogen and oxidative stress, High Blood Pressure Research 2013 Scientific Sessions, Sep. 2013.
47.	Yuya Horinouchi, Fiona A. Summers, Marilyn Ehrenshaft, Hitoshi Houchi, Toshiaki Tamaki, Kazuo Minakuchi and Ronald P. Mason : Cytotoxity evaluation of environmental chemicals via free radical detection using newly technique immuno-spin trapping, In-Cell Western and confocal microscopy, 49th Congress of the European Societies of Toxicology (EUROTOX), Sep. 2013.
48.	Takumi Sakurada, K. Miyako, Yuya Horinouchi, Kazuhiko Teraoka, T. Kujime, Kazuyoshi Kawazoe, Hitoshi Houchi, Toshiaki Tamaki and Kazuo Minakuchi : NITROSONIFEDIPINE, A PHOTODEGRADATION PRODUCT OF NIFEDIPINE, SUPPRESS THE PROGRESSION OF DIABETIC NEPHROPATHY WITH THE ENDOTHELIAL DYSFUNCTION, 11th EACPT Congress, Aug. 2013.
49.	Yuki Izawa-Ishizawa, Keisuke Ishizawa, Sakiko Doi, Yoshitaka Kihira, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : Rho-kinase is involved in inorganic phosphate-induced ERK1/2 activation in vascular smooth muscle cells, World Biotechnology Congress 2013, Jun. 2013.
50.	Yasumasa Ikeda, Hideaki Enomoto, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : The effect of dietary iron restriction against diabetic nephropathy in db/db mice, Experimental Biology 2013, Apr. 2013.
51.	Taisuke Nakayama, Hirotsugu Kurobe, Noriko Sugasawa, Hajime Kinoshita, Mayuko Higashida, Yuki Matsuoka, Yasushi Yoshida, Yoichiro Hirata, Mie Sakata, Mark Webster Maxfield, Yousuke Takahama, Masataka Sata, Toshiaki Tamaki, Tetsuya Kitagawa and Shuhei Tomita : Role of Macrophage-derived Hif-1a as a Mediator of Vascular Remodeling, American Heart Association Scientific Sessions 2012, Nov. 2012.
52.	Yasumasa Ikeda, Ken-ichi Aihara, Sumiko Yoshida, Masataka Sata, Masashi Akaike, Toshio Matsumoto and Toshiaki Tamaki : Heparin Cofactor II Promotes Angiogenesis in Response to Ischemic Hindlimb via an AMPK-eNOS-dependent Manner, American Heart Association Scientific Sessions 2012, Nov. 2012.
53.	Yusaku Maeda, Shuhei Tomita, Masaki Murakami, Hirotsugu Kurobe, Masaki Imanishi, Yasushi Yoshida, Yoichiro Hirata, Yoshitaka Kihira, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya, Tetsuya Kitagawa, Masataka Sata and Toshiaki Tamaki : Deficiency of Hypoxia Inducible Factor-1a in SM-22a-Expressing Bone Marrow-Derived Cells Alleviates Neointimal Formation Following Wire-induced Vascular Formation, American Heart Association Scientific Sessions 2012, Nov. 2012.
54.	Yasumasa Ikeda, Hideaki Enomoto, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Iron Restriction Prevents the Progression of Diabetic Nephropathy in db/db Mice, American Heart Association Scientific Sessions 2012, Nov. 2012.
55.	Masaki Imanishi, Shuhei Tomita, Keisuke Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Noriko Yamano, Yuki Izawa-Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Hypoxia-inducible Factor-1a in Vascular Smooth Muscle Cells Regulates Angiotensin -induced Vascular Remodeling and AT1 Receptor Expression in Mouse Aortic Media, American Heart Association Scientific Sessions 2012, Nov. 2012.
56.	Hideaki Enomoto, Yasumasa Ikeda, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Protective Effects of Iron-Restricted Food against Diabetic Nephropathy in db/db Mice, American Heart Association High Blood Pressure Research 2012, Sep. 2012.
57.	Shoko Fujii, Keisuke Ishizawa, Takumi Sakurada, Noriko Yamano, Yuki Izawa-Ishizawa, Masaki Imanishi, Asami Nuno, Yuta Suzuki, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Nitrosonifedipine, a Photodegradation Product of Nifedipine, Prevents the Progression of Diabetic Nephropathy in Type II Diabetic Mice, American Heart Association High Blood Pressure Research 2012, Sep. 2012.
58.	Mitsuru Takaku, Shuhei Tomita, Hirotsugu Kurobe, Akira Ushiyama, Ichiro Hashimoto, Toshiaki Tamaki and Hideki Nakanishi : PRECONDITIONING BY SYSTEMIC INTRODUCTION OF A PROLYL HYDROXYLASE INHIBITOR, DIMETHYLOXALYLGLYCINE,PROMOTES PREVENTION OF SKIN FLAP NECROSIS VIA HIF-1-INDUCED BONE MARROW-DERIVED PROGENITOR CELLS, 4thCongress of the World Union of Wound Healing Societies, Yokohama, Sep. 2012.
59.	Masaki Imanishi, Keisuke Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Noriko Yamano, Yuki Izawa-Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki and Shuhei Tomita : Hypoxia-inducible factor-1a deficiency in smooth muscle cell attenuates angiotensin -induced vascular remodeling in mice, ISOTT (International Society on Oxygen Transport to Tissue) 2012, Aug. 2012.
60.	Takumi Sakurada, Keisuke Ishizawa, Shoko Fujii, Yuki Izawa-Ishizawa, Masaki Imanishi, Asami Nuno, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Effects of nitrosonifedipine, a photodegradation product of nifedipine, on diabetic nephropathy in type II diabetic mice, Experimental Biology 2012, Apr. 2012.
61.	Yasumasa Ikeda, Hideaki Enomoto, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Iron restriction prevents progression of diabetic nephropathy, KEYSTONE SYMPOSIA 40th ANNIVERSARY 1972-2012 Complications of Diabetes: Mechanisms of Injury and Failure of Repair, Mar. 2012.
62.	Yusaku Maeda, Shuhei Tomita, Masaki Murakami, Hirotsugu Kurobe, Masaki Imanishi, Yasushi Yoshida, Yoichiro Hirata, Yoshitaka Kihira, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya, Tetsuya Kitagawa, Masataka Sata and Toshiaki Tamaki : Deficiency of Hypoxia Inducible Factor-1 in SM-22-Expressing Bone Marrow-Derived Cells Alleviates Neointimal Formation Following Wire-induced Vascular Formation, AHA SCIENTIFIC SESSIONS 2012, 2012.
63.	Masaki Imanishi, Shuhei Tomita, Keisuke Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Noriko Yamano, Yuki Izawa-Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Hypoxia-inducible Factor-1 in Vascular Smooth Muscle Cells Regulates Angiotensin -induced Vascular Remodeling and AT1 Receptor Expression in Mouse Aortic Media, AHA SCIENTIFIC SESSIONS 2012, 2012.
64.	Fujii Shoko, Keisuke Ishizawa, Takumi Sakurada, Noriko Yamano, Yuki Izawa-Ishizawa, Masaki Imanishi, Asami Nuno, Yuta Suzuki, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Nitrosonifedipine, a Photodegradation Product of Nifedipine, Prevents the Progression of Diabetic Nephropathy in Type II Diabetic Mice, HIGH BLOOD PRESSURE RESEARCH 2012 SCIENTIFIC SESSIONS, 2012.
65.	Masaki Imanishi, Keisuke Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Noriko Yamano, Yuki Izawa-Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki and Shuhei Tomita : Hypoxia-inducible factor-1 deficiency in smooth muscle cell attenuates angiotensin II-induced vascular remodeling in mice, The International Society on Oxygen Transport to Tissue 2012, 2012.
66.	Shuhei Tomita, Masaki Imanishi, Yoshitaka Kihira, Koichiro Tsuchiya and Toshiaki Tamaki : Angiotensin II-induced vascular remodeling is mediated by hypoxia-inducible factor-1 signaling pathway in vascular smooth muscle cells, The 33rd Naito Conference, 2012.
67.	Takumi Sakurada, Keisuke Ishizawa, Shoko Fujii, Yuki Izawa-Ishizawa, Masaki Imanishi, Asami Nuno, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Effects of nitrosonifedipine, a photodegradation product of nifedipine, on diabetic nephropathy in type II diabetic mice, Experimental Biology 2012, 2012.
68.	Masaki Imanishi, Keisuke Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Noriko Yamano, Yuki Izawa-Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki and Shuhei Tomita : Smooth Muscle Cell-Specific Hypoxia-Inducible Factor-1a Deficiency Attenuates Angiotensin II-Induced Vascular Remodeling in Mice, AHA scientific sessions 2011, Orlando, Nov. 2011.
69.	Soichiro Tajima, Yasumasa Ikeda, Noriko Yamano, Koichiro Tsuchiya, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Kazuyoshi Kawazoe, Shuhei Tomita, Kazuo Minakuchi and Toshiaki Tamaki : Inhibition of Adipocyte Hypertrophy by Deferoxiamine Diabetic KKAy mice, High Blood Pressure Research Scientific Sessions 2011 Scientific Sessions, Orlando, Sep. 2011.
70.	Kazuyuki Yamaguchi, Yoshitaka Kihira, Noriko Yamano, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya, Shuhei Tomita and Toshiaki Tamaki : Glucose Metabolism of Adipocytes is Regulated by Basic Fibroblast Growth Factor via Hypoxia-inducible Factor-1a, High Blood Pressure Research Scientific Sessions 2011 Scientific Sessions, Orlando, Sep. 2011.
71.	Masaki Imanishi, Keisuke Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Noriko Yamano, Yuki Izawa-Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki and Shuhei Tomita : Hypoxia-inducible Factor-1a Deficiency in Smooth Muscle Cells Suppresses Angiotensin -induced Vascular Remodeling in Mice, High Blood Pressure Research Scientific Sessions 2011 Scientific Sessions, Orlando, Sep. 2011.
72.	Yasumasa Ikeda, Ken-ichi Aihara, Sumiko Yoshida, Yoshitaka Kihira, Keisuke Ishizawa, Yuki Izawa-Ishizawa, Shuhei Tomita, Masataka Sata, Masashi Akaike, Shigeki Kato, Toshio Matsumoto and Toshiaki Tamaki : Heparin Cofactor Promotes Angiogenesis via an AMPK-eNOS Signaling Pathway, High Blood Pressure Research Scientific Sessions 2011 Scientific Sessions, Orlando, Sep. 2011.
73.	Yuki Izawa-Ishizawa, Keisuke Ishizawa, Takumi Sakurada, Masaki Imanishi, Shoko Fujii, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Angiotensin -induced Vascular Remodeling is Improved by Nitrosonifedipine, a Possible New Class Drug Against Oxidative Stress, High Blood Pressure Research Scientific Sessions 2011 Scientific Sessions, Orlando, Sep. 2011.
74.	Keisuke Ishizawa, Takumi Sakurada, Masaki Imanishi, Shoko Fujii, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Nitorosonifedipine is a new class drug to improves angiotensin II-induced vascular remodeling, European Society of Cardiology Congress 2011, Aug. 2011.
75.	Mitsuru Takaku, Shuhei Tomita, Hirotsugu Kurobe, Ichiro Hashimoto, Hideki Nakanishi and Toshiaki Tamaki : Preconditioning of mice with a PHD inhibitor, dimethyloaxylglycine, prevent skin flap necrosis, ISOTT (International Society on Oxygen Transport to Tissue) 2011, Georgetown, Jul. 2011.
76.	Shuhei Tomita, Yoshitaka Kihira, Noriko Yamano, Yuki Izawa-Ishizawa, Yasumasa Ikeda, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Characterization on mice lacking HIF1a gene in renal ischemia-reperfusion injury, ISOTT (International Society on Oxygen Transport to Tissue) 2011, Washington, D.C., Jul. 2011.
77.	Yasumasa Ikeda, Soichiro Tajima, Noriko Yamano, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Estrogen action on iron metabolism, ENDO 2011: The 93rd Annual Meeting & Expo, Boston, Jun. 2011.
78.	Shuji Kondo, S Matsuura, Yukiko Kinoshita, Ken-ichi Suga, Maki Urushihara, T Nagai, Toshiaki Tamaki and Shoji Kagami : The expression of NADPH oxidase and reactive oxygen species (ROS) production contribute to ureteric bud branching and nephrogenesis, World Congress of Nephrology 2011, Apr. 2011.
79.	Masaki Imanishi, Soichiro Tajima, Yoshitaka Kihira, Keisuke Ishizawa, Shuji Kondo, Shoji Kagami, Shuhei Tomita, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : Increment intracellular labile iron enhances Angiotensin-induced intracellular adhesion molecule-1 (ICAM-1) expression in human glomerular endothelial cells, World congress of Nephrology 2011, Vancouver, Apr. 2011.
80.	Masaki Imanishi, Keisuke Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Noriko Yamano, Yuki Izawa-Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki and Shuhei Tomita : Smooth Muscle Cell-specific Hypoxia-inducible Factor-1a Deficiency Attenuates Angiotensin II-induced Vascular Remodeling In Mice, AHA SCIENTIFIC SESSIONS 2011, 2011.
81.	Yuki Izawa-Ishizawa, Keisuke Ishizawa, Sakurada Takumi, Masaki Imanishi, Fujii Shoko, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Angiotensin II-induced Vascular Remodeling Is Improved By Nitrosonifedipine, A Possible New Class Drug, HIGH BLOOD PRESSURE RESEARCH 2011 SCIENTIFIC SESSIONS, 2011.
82.	Masaki Imanishi, Keisuke Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Noriko Yamano, Yuki Izawa-Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki and Shuhei Tomita : Hypoxia-inducible Factor-1 Deficiency In Smooth Muscle Cells Suppresses Angiotensin II-induced Vascular Remodeling In Mice, HIGH BLOOD PRESSURE RESEARCH 2011 SCIENTIFIC SESSIONS, 2011.
83.	Keisuke Ishizawa, Takumi Sakurada, Masaki Imanishi, Shoko Fujii, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Nitorosonifedipine is a new class drug to improve angiotensin II-induced vascular remodeling, ESC Congress 2011, 2011.
84.	Masaki Imanishi, Soichiro Tajima, Yoshitaka Kihira, Keisuke Ishizawa, Shuji Kondo, Shoji Kagami, Shuhei Tomita, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : INCREMENT INTRACELLULAR LABILE IRON ENHANCES ANGIOTENSIN II-INDUCED INTRACELLULAR ADHESION MOLECULE-1 (ICAM-1) EXPRESSION IN HUMAN GLOMERULAR ENDOTHELIAL CELLS, World Congress of Nephrology 2011, 2011.
85.	Toshiaki Tamaki, Kunihisa Yamaguchi, Yoshitaka Kihira, Yasumasa Ikeda, Keisuke Ishizawa, Koichiro Tsuchiya, Shuji Kondo, Shoji Kagami and Shuhei Tomita : Global gene expression analyses in renal ischemia-reperfusion injury (IRI) from mice lucking Hif-1a gene, ASN RENAL WEEK 2010 EXHIBIT, Nov. 2010.
86.	Koichiro Tsuchiya, Yuya Horinouchi, Soichiro Tajima, Yoshitaka Kihira, Yasumasa Ikeda, Keisuke Ishizawa, Yoshiyuki Yoshimura, Shuhei Tomita, Shuichi Hamano and Toshiaki Tamaki : Antioxidant effects of photodegradation product of nifedipine, 17th Annual Meeting of the Society for Free Radical Biology and Medicine (SFRBM 2010), Nov. 2010.
87.	Matsuura Sato, Shuji Kondo, Ken-ichi Suga, Yukiko Kinoshita, Maki Urushihara, Toshiaki Tamaki and Shoji Kagami : Reactive oxygen species (ROS) produced by NADPH oxidase contribute ureteric bud branching and nephrogenesis, ASN 2010, Colorado, Nov. 2010.
88.	Shuhei Tomita, Masahisa Urata, Yayoi Fukuhara, Yoshitaka Kihira, Yasumasa Ikeda, Keisuke Ishizawa, Koichiro Tsuchiya, Tetsuya Kitagawa and Toshiaki Tamaki : Endothelial-targeted hypoxia-inducible factor-1b (HIF-1b) loss-of function alleviates the monocrotaline-induced pulmonary hypertension in mice, American Heart Association Scientific Sessions 2010, Chicago, Nov. 2010.
89.	Keisuke Ishizawa, Masaki Imanishi, Yuya Horinouchi, Yayoi Fukuhara, Yuki Izawa-Ishizawa, Yasumasa Ikeda, Yoshitaka Kihira, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Nitroso-nifedipine is a new class drug to protect endothelial function for overcoming organ damage, International Society of Hypertension 2010, Vancouver, Sep. 2010.
90.	Soichiro Tajima, Yasumasa Ikeda, Noriko Yamano, Koichiro Tsuchiya, Yoshitaka Kihira, Keisuke Ishizawa, Kazuyoshi Kawazoe, Shuhei Tomita, Kazuo Minakuchi and Toshiaki Tamaki : IRON DERIVATION AMELIORATES GLUCOSE TOLERANCE THROUGH REDUCTION OF OXIDATIVE STRESS AND INFLAMMATION IN DIABETIC KKAY MICE, 2010 American Physiological Society Conference Inflammation, Immunity and Cardiovascular Disease, Aug. 2010.
91.	Sato Matsuura, Shuji Kondo, Ken-ichi Suga, Yukiko Kinoshita, Toshiaki Tamaki and Shoji Kagami : Expression and localization of focal adhesion proteins in the developing rat kidney, The 15th Congress of the International Pediatric Nephrology Association, Aug. 2010.
92.	Yayoi Fukuhara, Shuhei Tomita, Yuko Imamura, Yuya Horinouchi, Masaki Imanishi, Takumi Sakurada, Tetsuya Kitagawa and Toshiaki Tamaki : Role of HIF-1b in endothelial cells in monocrotaline-induced pulmonary hypertension in mice, 16th World Congress on Basic and Clinical Pharmacology, Jul. 2010.
93.	Yoshitaka Kihira, Shuhei Tomita, Yasumasa Ikeda, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Basic fibroblast growth factor upregulates hypoxia inducible factor 1 and glucose transporter 1 in adipose cells, The 16th World Congress of Basic and Clinical Pharmacology (WorldPharma 2010), Copenhagen, Jul. 2010.
94.	Soichiro Tajima, Yasumasa Ikeda, Yoshitaka Kihira, Keisuke Ishizawa, Kazuyoshi Kawazoe, Shuhei Tomita, Kazuo Minakuchi, Toshiaki Tamaki and Koichiro Tsuchiya : Deferoxamine, an iron chelator, promotes angiogenesis after ischemic hind limb through Akt-eNOS-dependent pathway, The 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide, Jun. 2010.
95.	Keisuke Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Toshiaki Tamaki and Koichiro Tsuchiya : Metabolism of quercetin in vivo and its protective effect against cardiovascular diseases, 2nd International On-Board Symposium: Human Health, Energy and Environment, May 2010.
96.	Yasumasa Ikeda, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Deferoxamine, an iron chelator, promotes angiogenesis after ischemic hind limb through Akt-eNOS-dependent pathway, XX World Congress ISHR 2010 KYOTO, May 2010.
97.	Toshiaki Tamaki, Kunihisa Yamaguchi, Yoshitaka Kihira, Yasumasa Ikeda, Keisuke Ishizawa, Koichiro Tsuchiya and Shuhei Tomita : Amelioration of acute tubular necrosis in ischemic acute renal failure was impaired in mice lucking hypoxia inducible factor-1 gene, ISN (International Society of Nephrology) nexus sympojium 2010, Apr. 2010.
98.	Souichiro Tajima, Yasumasa Ikeda, Yoshitaka Kihira, Keisuke Ishizawa, Kazuyoshi Kawazoe, Shuhei Tomita, Kazuo Minakuchi, Toshiaki Tamaki and Koichiro Tsuchiya : Deferoxamine, an iron chelator, promotes angiogenesis after ischemic hind limb through Akt-eNOS-dependent pathway, The 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide, Kyoto, Apr. 2010.
99.	Shuji Kondo, Ken-ichi Suga, sato Matsuura, Yukiko Kinoshita, Maki Urushihara, Toshiaki Tamaki and Shoji Kagami : Enhanced expression of Hic-5 is involved in the development of human and rat mesangioproliferative glomerulonephritis, ISN-Nexus Kyoto Symposium 2010, Apr. 2010.
100.	Gang Liu, Kayoko Miyata, Hirofumi Hitomi, Li Yao, Guang-Ping Sun, Yuki Suzaki, Naohisa Hosomi, Hideyasu Kiyomoto, Daisuke Nakano, Toshiaki Tamaki, Masanori Yoshizumi and Akira Nishiyama : Involvement of mineralocorticoid receptor in high glucose-induced big mitogen-activated protein kinase 1 activation and mesangial cell proliferation., Journal of Hypertension, Vol.28, No.3, 536-542, Mar. 2010. (要約) We previously demonstrated that high glucose-induced cell proliferation in cultured rat mesangial cells (RMCs) is mediated through activation of big mitogen-activated protein kinase 1 (BMK1). We also found that, in aldosterone-treated rats, mesangial proliferation is associated with BMK1 activation and that these effects were prevented by treatment with a selective mineralocorticoid receptor antagonist, eplerenone. In this study, we investigated the contribution of mineralocorticoid receptors to high glucose-induced BMK1 activation and cell proliferation in RMCs. BMK1 phosphorylation was measured by western blot analysis. Cell proliferation was evaluated by [3H]-thymidine incorporation. High glucose treatment (15.5 mmol/l) increased BMK1 phosphorylation in both the nucleus and cytosol of RMCs. High glucose-induced BMK1 phosphorylation was attenuated by pretreatment with eplerenone (10 micromol/l), mineralocorticoid receptor small interfering RNA or PD98059 (100 micromol/l), a specific inhibitor of extracellular signal-regulated kinase kinase (MEK). Likewise, high glucose-induced increases in [H]-thymidine incorporation were prevented by eplerenone or PD98059 and transfection of dominant-negative MEK5, which is the upstream regulator of BMK1. These results suggest that mineralocorticoid receptors are involved in high glucose-induced BMK1 phosphorylation and cell proliferation. The inhibitory actions of mineralocorticoid receptor antagonists may contribute to their preventive effects on diabetic nephropathy, which have been reported in recent clinical studies. (キーワード) Animals / Base Sequence / Cell Proliferation / Cells, Cultured / Enzyme Activation / Glomerular Mesangium / Glucose / Male / Mitogen-Activated Protein Kinase 7 / Phosphorylation / RNA, Small Interfering / Rats / Rats, Sprague-Dawley / Receptors, Mineralocorticoid (出版サイトへのリンク) ● Publication site (DOI): 10.1097/HJH.0b013e3283346b62 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20090557 ● Search Scopus @ Elsevier (PMID): 20090557 ● Search Scopus @ Elsevier (DOI): 10.1097/HJH.0b013e3283346b62 (DOI: 10.1097/HJH.0b013e3283346b62, PubMed: 20090557)
101.	Koichiro Tsuchiya, Soichiro Tajima, Keisuke Ishizawa, Shuhei Tomita, Yoshitaka Kihira, Yasumasa Ikeda, Yoshiyuki Yoshimura, Shuichi Hamano and Toshiaki Tamaki : Effect of Angiotensin II on the intracellular labile iron concentration in HGECs, 16th Annual Meeting of the Society for Free Radical Biology and Medicine (SFRBM 2009), Nov. 2009.
102.	Yasumasa Ikeda, Kaori Sato, David Pimentel, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Flora Sam, Toshiaki Tamaki and Kenneth Walsh : LKB1 gene in myocytes plays a critical role to regulate the coordinated cardiac growth and capillary development, American Heart Association Scientific Sessions 2009, Orlando, Nov. 2009.
103.	Yasumasa Ikeda, Kaori Sato, David Pimentel, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Flora Sam, Toshiaki Tamaki and Kenneth Walsh : LKB1 gene in myocytes plays a critical role to regulate the coordinated cardiac growth and capillary development, American Heart Association Scientific Sessions 2009, Orlando, Nov. 2009.
104.	田島壮一郎, Koichiro Tsuchiya, Yuya Horinouchi, 石澤啓介, 寺岡和彦, 冨田修平, 川添和義, 芳地一, Toshiaki Tamaki and 水口和生 : ANGIOTENSIN II INCREASED INTRACELLULAR LABILE IRON IN THE PRESENCE OF TRANSFERRIN IN HGEC, Basic & Clinical Pharmacology & Toxicology, Vol.105, 127, 2009.
105.	Kunihisa Yamaguchi, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya, Shuji Kondo, Shoji Kagami and Toshiaki Tamaki : Hypoxia-Inducible Factor-1α ameliorates ischemic acute renal failure and has a relation with a recovery from acute tubular necrosis, 41th ASN annual meeting, Philadelphia, Nov. 2008.
106.	Toshiaki Tamaki, Keisuke Ishizawa, Kunihisa Yamaguchi, Shuji Kondo, Shoji Kagami, Fukuhara Yayoi, Yuya Horinouchi and Koichiro Tsuchiya : Nitoroso-nifedipine is a new class drug to protect kidney against oxidative stress, 41th ASN annual meeting, Philadelphia, Nov. 2008.
107.	Yuya Horinouchi, Koichiro Tsuchiya, 石澤啓介, 田島壮一郎, 元林有紀, 山口邦久, 川添和義, Kazuo Minakuchi and Toshiaki Tamaki : Endothelial cell protective activity of nitorosonifedipine, Biomedical Redox Navigation (EPR2008), Fukuoka, Sep. 2008.
108.	Koichiro Tsuchiya, Soichiro Tajima, Mai Hamamoto, Hideki Ohnishi, Yuki Motobayashi, Yuya Horinouchi, Kunihisa Yamaguchi, Keisuke Ishizawa, Kazuyoshi Kawazoe, Kazuo Minakuchi and Toshiaki Tamaki : Effect of angiotensin II on iron (II) turnover in HGEC, Biomedical Redox Navigation (EPR2008), Fukuoka, Sep. 2008.
109.	Yuya Horinouchi, Koichiro Tsuchiya, Keisuke Ishizawa, Soichiro Tajima, Yuki Motobayashi, Kunihisa Yamaguchi, Kazuyoshi Kawazoe, Kazuo Minakuchi and Toshiaki Tamaki : Endotherial cell protective activity of nitrosonifedipine, Biomedical Redox Navigation (EPR2008), Fukuoka, Sep. 2008.
110.	Yuki Motobayashi, Keisuke Ishizawa, Yuki Izawa-Ishizawa, Sakiko Orino, Dorjsuren Narantungalag, Kunihisa Yamaguchi, Kazuo Minakuchi and Toshiaki Tamaki : Inhibitory effects of adiponectin on cell migration induced by insulin-like growth factor-1 in vascular smooth muscle cells, The IXth World Conference on Clinical Pharmacology and Therapeutics, Québec City, Jul. 2008.
111.	Toshiaki Tamaki, Kunihisa Yamaguchi, Narantungalag Dorjsuren, Yayoi Fukuhara, Yuya Horinouchi, Yuki Motobayashi, Koichiro Tsuchiya and Keisuke Ishizawa : Olmesartan inhibits the TNF-α-induced cytotoxicity in human glomerular endothelial cells, ISN Nexus Symposium on Diabetes & the Kidney, Dublin, Jun. 2008.
112.	Keisuke Ishizawa, Narantungalag Dorjsuren, Yuki Izawa-Ishizawa, Teppei Tsuneishi, Yuki Motobayashi, Hideki Ohnishi, Kunihisa Yamaguchi, Koichiro Tsuchiya and Toshiaki Tamaki : Inhibitory effects of olmesartan on TNF-α-induced cytotoxicity in human glomerular endothelial cells, 40th ASN annual meeting, San Francisco, Nov. 2007.
113.	Maki Urushihara, Masanori Takamatsu, Maki Shimizu, Shuji Kondo, Akiko Kitamura, Yukiko Kinoshita, Keisuke Ishizawa, Toshiaki Tamaki and Shoji Kagami : The role of extracellular signal regulated kinase 5 in the accumulation of collagen matrix in rat mesangioproliferative glomerulonephritis, 40th ASN annual meeting, San Francisco, CA, Nov. 2007.
114.	Koichiro Tsuchiya, Satoshi Iwanaga, Hideki Ohnishi, Yayoi Fukuhara, Chiaki Taoka, Soichiro Tajima, Yuya Horinouchi and Toshiaki Tamaki : In vivo and in vitro studies on NO formation from iron-quercetin-nitrite complexes, Second International Role of Nitrite in Physiology, Pathophysiology and Therapeutics Meeting, Bethesda, Maryland, Sep. 2007.
115.	Keisuke Ishizawa, Erika Miki, Arisa Hironaga, Koichiro Tsuchiya, Maki Urushihara, Shoji Kagami and Toshiaki Tamaki : Angiotensin II receptor blocker inhibits PDGF-induced cell migration in rat mesangial cells, 39th ASN annual meeting 2006, San Diego, Nov. 2006.
116.	Maki Urushihara, Masanori Takamatsu, Maki Shimizu, Shuji Kondo, Toshiaki Tamaki and Shoji Kagami : Extracellular signal regulated kinase 5 induces mesangial cell survival in rat progressive mesangioproliferative glomerulonephritis, 39th ASN annual meeting 2006, San Diego, Nov. 2006.
117.	Koichiro Tsuchiya, Yuya Horinouchi, Yasuhisa Kanematsu, Shinji Abe, Hideki Ohnishi, Soichiro Tajima, Keisuke Ishizawa, Toshiaki Tamaki and Yoshiharu Takiguchi : Production of nitrosonifedipine radical from nifedipine and its antioxidative activity in cultured cells, 13th annual meeting of society of free radical and biology of medicine, Denver, Nov. 2006.
118.	Hideki Ohnishi, Koichiro Tsuchiya, Yasuhisa Kanematsu, Shinji Abe, Soichiro Tajima and Toshiaki Tamaki : Effects of quercetin on NO production from nitrite at physiological conditions, 20th Scientific Meeting of the International Soiciety of Hypertension, Fukuoka, Japan, Oct. 2006.
119.	Hiroyuki Sakakibara, Yuki Izawa, Jun-ichiro Nakajima, Shujiro Seo, Toshiaki Tamaki, Yoshichika Kawai and Junji Terao : Antidepressant effects of polyphenol rich herbal medicine, Ginkgo biloba, extracts in behavioral models, 232 nd American Chemical Society Meeting & Exposition, San Francisco, Sep. 2006.
120.	Koichiro Tsuchiya, Yasuhisa Kanematsu, Keisuke Ishizawa, Shinji Abe, Hideki Ohnishi, Soichiro Tajima, Kazuyoshi Kawazoe, Yoshiharu Takiguchi and Toshiaki Tamaki : Dietary nitrite is an alternative source of NO in vivo, International Society for Radical Research 13th Biennial Congress, Davos, Switzerland, Aug. 2006.
121.	Hirotsugu Kurobe, Yuki Izawa, Y Fukuhara, Tamotsu Kanbara, A Kurushima, Ken-ichi Aihara, Masashi Akaike, Masashi Kano, Takashi Kitaichi, Yutaka Masuda, Hiroyuki Azuma, Toshiaki Tamaki, Toshio Matsumoto, Tetsuya Kitagawa, Shuhei Tomita and Masanori Yoshizumi : HIF-ARNT transcriptional system in Tcells has a pivotal role in vascular inflammation and remodeling, XIL International Symposium on Atherosclerosis, Italy, Jun. 2006.
122.	Yoshiyasu Terashima, Kazuo Mori, Takuji Kawano and Toshiaki Tamaki : Four-hour student workshop for introduction to PBL tutorial learning program, 6th Asia Pacific Conference on Problem-Based Learning, Tokyo, May 2006.
123.	Hirotsugu Kurobe, Yuki Izawa, Yayoi Fukuhara, Tamotsu Kanbara, Ken-ichi Aihara, Masashi Akaike, Hiroyuki Azuma, Tetsuya Kitagawa, Toshiaki Tamaki, Toshio Matsumoto, Masaki Ueno, Shuhei Tomita and Masanori Yoshizumi : T Cell-specific HIF-1α-deficient Mice, but Not ARNT-deficient Mice, Exhibit Exacerbated Inflammation and Vascular Remodeling in Response to Cuff Injury, American Heart Association 2005 Scientifc Sessions, Dallas, Nov. 2005.
124.	Toshiaki Tamaki, Yasuhisa Kanematsu, Yuki Izawa, Hideki Ohnishi, Yuki Motobayashi, Shoji Kagami and Koichiro Tsuchiya : Chronic oral administration of nitrite restores circulating NO level and improves renal injury in L-NAME treated rats, 38th ASN annual meeting, Philadelphia, Nov. 2005.
125.	Keisuke Ishizawa, Rika Sugimoto, Yuki Izawa, Koichiro Tsuchiya, Kazuo Minakuchi and Toshiaki Tamaki : The inhibitory effect of adiponectin on migration and proliferation induced by PDGF in rat mesangial cells, 38th ASN annual meeting, Philadelphia, Nov. 2005.
126.	Maki Shimizu, Shuji Kondo, Maki Urushihara, Masanori Takamatsu, Toshiaki Tamaki and Shoji Kagami : Reactive Oxygen Species (ROS) is Pivotal Mediator for Glomerular Epithelial-Mesenchymal Transition (EMT) in Experimental Progressive Glomerulonephritis (GN), 38th ASN annual meeting, Philadelphia, Nov. 2005.
127.	Hiroyuki Sakakibara, Kaori Ishida, Yuki Izawa, Yuko Minami, Satomi Saito, Yoshichika Kawai, Butterweck Veronika, Toshiaki Tamaki, Yutaka Nakaya and Junji Terao : Effects of Ginkgo biloba Extract on Rat brain Function, 2nd International Conference on Polyphenols and Health, California Davis, Davis, Oct. 2005.
128.	Soichiro Tajima, Koichiro Tsuchiya, Hideki Ohnishi, Yasuhisa Kanematsu, Masanori Yoshizumi, Toshiaki Tamaki, Mason P. Ronald and Yoshiharu Takiguchi : Immunochemical Dection of Thioredoxin-Derived Radicals Formed by Reaction with Hydrogen Peroxide, EPR 2005, Columbus, OH, Sep. 2005.
129.	Koichiro Tsuchiya, Kaori Akai, Akira Tokumura, Shinji Abe, Toshiaki Tamaki, Yoshiharu Takiguchi and Kenji Fukuzawa : Oxygen Radicals Photo-induced by Ferric Nitrilotriacetate(FE-NTA) Complex, EPR 2005, Columbus, OH, Sep. 2005.
130.	Hiroyuki Sakakibara, Kaori Ishida, Yuki Izawa, Yuko Minami, Saito Saromi, Yoshichika Kawai, Butterweck Veronika, Toshiaki Tamaki, Yutaka Nakaya and Junji Terao : Effects of forced swimming stress on rat brain function, 2005 COE International Conference ''Biological Mechanism for Stress Control'', Tokushima, Aug. 2005.
131.	Keisuke Ishizawa, Rika Sugimoto, Yuki Izawa, Kazuo Minakuchi, Koichiro Tsuchiya and Toshiaki Tamaki : Adiponectin inhibits PDGF-induced migration and proliferation in rat mesangial cells, 第10回アディポサイエンス研究会シンポジウム(第10回記念国際シンポジウム), Osaka, Aug. 2005.
132.	Toshiaki Tamaki, Masumi Okamoto, Yasuhisa Kanematsu, Yuki Izawa, Shoji Kagami, Shuji Kondo, Masanori Yoshizumi and Koichiro Tsuchiya : Dietary dose of nitrite attenuates L-NAME-induced renal injury in rats, 3rd World Congress of Nephrology, Singapore, Jun. 2005.
133.	Masanori Yoshizumi, Keisuke Ishizawa, Yuki Izawa, Chieko Miki, Yoshiko Fujita, Yasuhisa Kanematsu, Koichiro Tsuchiya and Toshiaki Tamaki : Aldosterone stimulates vascular smooth muscle cell proliferation through big mitogen-activated protein kinase1 activation, 16th scientific meeting of the interamerican society of hypertension, Cancun, Mexico, Apr. 2005.
134.	Toshiaki Tamaki, Masumi Okamoto, Yasuhisa Kanematsu, Yuki Izawa, Shoji Kagami, Shuji Kondo, Maki Shimizu, Masanori Yoshizumi and Koichiro Tsuchiya : Nitrite-derived nitric oxide formation following ischemia-reperfusion injury in rat kidney, 37th ASN annual meeting, St. Louis, MO, Oct. 2004.
135.	Shuji Kondo, Maki Shimizu, Koichiro Tsuchiya, Masanori Yoshizumi, Toshiaki Tamaki, Hiroshi Kawachi, Fujio Shimizu, Quinn T Mark, Lambeth J David, Yasuhiro Kuroda and Shoji Kagami : Add-on the antioxidant, probucol to angiotensin II type I receptor antagonist (ARB) arrests the progressive, St. Louis, MO, Oct. 2004.
136.	Shuji Kondo, M Shimizu, Koichiro Tsuchiya, Masanori Yoshizumi, Toshiaki Tamaki, H Kawachi, F Shimizu, Quinn MT, Lambeth DJ, Yasuhiro Kuroda and Shoji Kagami : Add-On the antioxidant,probucol to angiotensin 2 Type I receptor antagonist (ARB) arrests the progressive glomerulonephritis (GN) in the rat, 37th Annual meeting of American Society of Nephrology, St. Louis, 2004.
137.	Toshiaki Tamaki, K Kirima, Masato Okamoto, S. Kondo, Shoji Kagami, Masanori Yoshizumi and Koichiro Tsuchiya : Oral nitrite increases the blood oxide and protects L-NAME-induced renal injury in rats, 36th Annual meeting of American Society of Nephrology, San Diego, 2003.

国内講演発表:

1.	乙田敏城, 湯浅智之, 関根明子, 上元良子, 森博康, 原倫世, 田蒔基行, 玉置俊晃, 松久宗英, 粟飯原賢一 : SGLT2 阻害薬投与による蛋白尿減少および炎症抑制効果の検討, 第 65 回日本糖尿病学会年次学術集会, 2022年5月.
2.	乙田敏城, 湯浅智之, 関根明子, 上元良子, 森博康, 原倫世, 田蒔基行, 玉置俊晃, 松久宗英, 粟飯原賢一 : SGLT2阻害薬投与による蛋白尿減少および炎症抑制効果の検討, 第65回日本糖尿病学会年次学術集会, 2022年5月.
3.	乙田敏城, 湯浅智之, 関根明子, 上元良子, 森博康, 田蒔基行, 玉置俊晃, 松久宗英, 粟飯原賢一 : SGLT2阻害薬の投与が蛋白尿減少効果をもたらす要因の検討, 第6回日本糖尿病・生活習慣病ヒューマンデータ学会, 2021年12月.
4.	池田康将, 濱野裕章, 堀ノ内裕也, 宮本理人, 玉置俊晃, 土屋浩一郎 : シスプラチン誘発性腎毒性における鉄依存性細胞死の役割の検討, 第64回日本腎臓学会学術集会, 2021年6月.
5.	池田康将, 濱野裕章, 合田光寛, 福島圭穣, 岸誠司, 中馬真幸, 座間味義人, 宮本理人, 石澤啓介, 藤野裕道, 粟飯原賢一, 土屋浩一郎, 玉置俊晃 : シスプラチン起因性腎障害の予防薬の探索・同定, 第94回日本薬理学会年会, 2021年3月.
6.	池田康将, 濱野裕章, 合田光寛, 福島圭穣, 岸誠司, 石澤啓介, 土屋浩一郎, 玉置俊晃 : シスプラチン起因性腎障害を予防する既存薬の同定, 第63回日本腎臓学会学術総会, 2020年8月.
7.	濱野裕章, 池田康将, 合田光寛, 福島圭穣, 岸誠司, 武智研志, 中馬真幸, 座間味義人, 堀ノ内裕也, 宮本理人, 藤野裕道, 石澤啓介, 土屋浩一郎, 玉置俊晃 : シスプラチン誘発性腎障害を予防する既存薬物の同定, 第260回徳島医学会学術集会(令和元年度冬期), 2020年2月.
8.	池田康将, 堀ノ内裕也, 濱野裕章, 石澤啓介, 土屋浩一郎, 玉置俊晃 : シスプラチン腎障害における鉄依存性細胞死の検討, 第29回日本循環薬理学会/第55回高血圧関連疾患モデル学会合同学会, 2019年11月.
9.	堀ノ内裕也, 池田康将, 濱野裕章, 土屋浩一郎, 玉置俊晃 : 慢性腎不全関連サルコペニアにおける鉄代謝異常, 第6回日本サルコペニア・フレイル学会大会, 2019年11月.
10.	近藤友宏, 宮本理人, 福田恵介, 高橋梨恵, 堀ノ内裕也, 池田康将, 玉置俊晃, 土屋浩一郎 : スダチ果皮香気成分由来物質による糖脂質代謝の影響, 第58回中国四国支部学術大会, 2019年11月.
11.	堀ノ内裕也, 池田康将, 濱野裕章, 今西正樹, 福島圭穣, 合田光寛, 武智研志, 宮本理人, 石澤有紀, 座間味義人, 藤野裕道, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 慢性腎不全関連骨格筋萎縮における鉄代謝異常, 第92回日本薬理学会年会, 2019年3月.
12.	池田康将, 佐藤明穂, 堀ノ内裕也, 石澤有紀, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 鉄蓄積は骨格筋分化を抑制する, 第92回日本薬理学会年会, 2019年3月.
13.	堀ノ内裕也, 池田康将, 玉置俊晃 : 疾患における鉄の意義と治療応用, 第92回日本薬理学会年会シンポジウム2:必須微量金属研究のパラダイムシフト, 2019年3月.
14.	堀ノ内裕也, 池田康将, 渡邉大晃, 濱野裕章, 石澤有紀, 今西正樹, 座間味義人, 武智研志, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃 : マクロファージフェリチン欠損は肥満・糖尿病における脂肪炎症を抑制する, 第48回日本心脈管作動物質学会, 2019年2月.
15.	堀ノ内裕也, 池田康将, 玉置俊晃 : 肥満・糖尿病における鉄制御の意義, 第48回日本心脈管作動物質学会シンポジウム4:心疾患腎代謝疾患の制御因子としての微量金属栄養素「鉄」の新たな展開, 2019年2月.
16.	堀ノ内裕也, 池田康将, 福島圭穣, 濱野裕章, 今西正樹, 石澤有紀, 座間味義人, 武智研志, 藤野裕道, 石澤啓介, 土屋浩一郎, 玉置俊晃 : リアルワールドビッグデータを活用した新規腎保護薬の探索, 第28回日本医療薬学会年会, 2018年11月.
17.	井上陽加, 宮本理人, 服部真奈, 池田康将, 玉置俊晃, 土屋浩一郎 : 亜硝酸塩による脂肪組織への抗肥満的な影響, 第134回日本薬理学会近畿部会, 2018年11月.
18.	堀ノ内裕也, 池田康将, 濱野裕章, 今西正樹, 福島圭穣, 合田光寛, 武智研志, 宮本理人, 石澤有紀, 座間味義人, 藤野裕道, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 慢性腎不全関連サルコペニアにおける鉄の関与, 第134回日本薬理学会近畿部会, 2018年11月.
19.	堀ノ内裕也, 池田康将, 福島圭穣, 石澤有紀, 藤野裕道, 玉置俊晃 : リアルワールドデータを活用した新規腎保護薬の探索, 第48回日本腎臓学会西部学術大会, 2018年9月.
20.	池田康将, 玉置俊晃 : シンポジウム1「腎疾患(CKD)の治療と研究の最前線」慢性腎臓病における鉄代謝の意義と治療応用, 第48回日本腎臓学会西部学術大会, 2018年9月.
21.	堀ノ内裕也, 池田康将, 渡邉大晃, 濱野裕章, 石澤有紀, 今西正樹, 武智研志, 座間味義人, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃 : マクロファージ鉄の肥満・糖尿病における役割第42回日本鉄バイオサイエンス学会学術集会 2018/9/2 石川県金沢医科大学病院北辰講堂, 第42回日本鉄バイオサイエンス学会学術集会, 2018年9月.
22.	石澤有紀, 鍵本優有, 今西正樹, 岩田悠佑, 鈴木琴子, 堀ノ内裕也, 武智研志, 座間味義人, 池田康将, 石澤啓介, 玉置俊晃 : 第40回徳島医学会賞受賞講演動脈硬化性疾患発症に対するケルセチンの効果, 第257回徳島医学会学術集会(平成30年度夏季), 2018年8月.
23.	土屋浩一郎, 宮本理人, 濱野修一, 堀ノ内裕也, 池田康将, 玉置俊晃, 津田勝範 : 抗マラリア薬artesunateからの鉄依存活性酸素生成メカニズムの検討, 第71回日本酸化ストレス学会，第18回日本NO学会合同学術集会, 2018年5月.
24.	座間味義人, 三井茉綸, 石澤有紀, 武智研志, 今西正樹, 堀ノ内裕也, 福島圭穣, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 有害事象自発報告データベースを活用したベバシズマブの抗腫瘍効果を減弱させる薬剤の探索研究, 日本薬学会第138年会, 2018年3月.
25.	新村貴博, 座間味義人, 石澤有紀, 今西正樹, 武智研志, 福島圭穣, 堀ノ内裕也, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : ドラッグリポジショニング手法を用いた心肺蘇生後脳症治療薬の探索, 日本薬学会第138年会, 2018年3月.
26.	Yasumasa Ikeda, Yuya Horinouchi, Yuki Izawa-Ishizawa and Toshiaki Tamaki : Factor Xa Inhibitor Exerts a Protective Effect against Renal Injury, 第82回日本循環器学会学術集会, Mar. 2018.
27.	堀ノ内裕也, 池田康将, 福島圭穣, 濱野裕章, 今西正樹, 石澤有紀, 座間味義人, 藤野裕道, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 大規模医療情報データベース解析と基礎研究の融合による新規腎保護薬の探索, 第256回徳島医学会学術集会(平成29年度冬期), 2018年2月.
28.	石澤有紀, 鍵本優有, 今西正樹, 岩田悠佑, 堀ノ内裕也, 武智研志, 座間味義人, 池田康将, 石澤啓介, 玉置俊晃 : マウス大動脈瘤形成に対するケルセチンの効果, 第256回徳島医学会学術集会(平成29年度冬期), 2018年2月.
29.	今西正樹, 近藤正輝, 田中恭平, 生藤来希, 村井陽一, 座間味義人, 武智研志, 堀ノ内裕也, 石澤有紀, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : Febuxostatの尿酸合成抑制作用とは独立した血管線維化抑制機構の解明, 第256回徳島医学会学術集会(平成29年度冬期), 2018年2月.
30.	武智研志, 座間味義人, 今西正樹, 堀ノ内裕也, 石澤有紀, 池田康将, 玉置俊晃, 石澤啓介, 楊河宏章 : てんかん誘発性精神症状の行動学的解析および治療薬の探索と作用機序の解明, 第256回徳島医学会学術集会(平成29年度冬期), 2018年2月.
31.	新村貴博, 座間味義人, 石澤有紀, 今西正樹, 武智研志, 福島圭穣, 堀ノ内裕也, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 大規模医療情報を活用した心肺停止患者に対するニコランジルの有効性に関する検討, 第256回徳島医学会学術集会(平成29年度冬期), 2018年2月.
32.	堀ノ内裕也, 池田康将, 福島圭穣, 今西正樹, 石澤有紀, 座間味義人, 藤野裕道, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 第Xa因子阻害剤の腎保護効果, 第47回日本心脈管作動物質学会, 2018年2月.
33.	宮本理人, 梅本果奈, 上島沙弥香, 友成奈央実, 土橋有希, 池田康将, 玉置俊晃, 土屋浩一郎 : 食後生じるAMPKの新たな翻訳後修飾を介した代謝制御機構, 心脈管作動物質学会, 2018年2月.
34.	堀ノ内裕也, 池田康将, 福島圭穣, 石澤有紀, 藤野裕道, 玉置俊晃 : 医療ビッグデータを活用した腎保護薬の探索, 2017年度肥満・糖尿病クラスター・ミニリトリート, 2018年2月.
35.	堀ノ内裕也, 池田康将, 福島圭穣, 今西正樹, 石澤有紀, 座間味義人, 藤野裕道, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 第Xa因子阻害薬の腎保護効果, 第10回心・血管クラスター・ミニリトリート, 2017年.
36.	別所将弘, 村上圭史, 藤猪英樹, 津田勝範, 宮本理人, 土屋浩一郎, 池田康将, 玉置俊晃, 濱野修一 : Actinomyces spp. による硝酸イオンの還元と生理作用の検討, 第41回徳島県医学検査学会, 2017年12月.
37.	日野咲季子, 座間味義人, 石澤有紀, 今西正樹, 武智研志, 堀ノ内裕也, 池田康将, 玉置俊晃, 石澤啓介 : 大規模医療情報を活用した薬剤性腎障害に対する予防薬の探索, 西日本医学生学術フォーラム2017, 2017年12月.
38.	岩田悠佑, 石澤有紀, 鍵本優有, 鈴木琴子, 堀ノ内裕也, 池田康将, 石澤啓介, 玉置俊晃 : マウス大動脈瘤形成に対するケルセチンの効果, 西日本医学生学術フォーラム2017, 2017年12月.
39.	石澤有紀, 鍵本優有, 今西正樹, 堀ノ内裕也, 鈴木琴子, 岩田悠佑, 座間味義人, 武智研志, 池田康将, 玉置俊晃, 石澤啓介 : ケルセチンによる動脈硬化性疾患発症に対する予防効果の検討, 第27回日本循環薬理学会, 2017年12月.
40.	新村貴博, 座間味義人, 石澤有紀, 今西正樹, 武智研志, 福島圭穣, 堀ノ内裕也, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 大規模医療情報を用いて新規心肺蘇生後症候群治療薬の開発を志向したドラッグリポジショニング研究, 第38回日本臨床薬理学会学術総会, 2017年12月.
41.	座間味義人, 石澤有紀, 新村貴博, 武智研志, 今西正樹, 堀ノ内裕也, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 臨床薬理学集中講座修了後の研究活動∼大規模医療情報を活用したドラッグリポジショニング研究を中心に∼, 第38回日本臨床薬理学会学術総会臨床薬理学集中講座フォローアップ・セミナー, 2017年12月.
42.	渡邉大晃, 池田康将, 濱野裕章, 堀ノ内裕也, 石澤有紀, 今西正樹, 座間味義人, 武智研志, 宮本理人, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 肥満・糖尿病におけるマクロファージ鉄制御機構の検討, 第132回日本薬理学会近畿部会, 2017年11月.
43.	新村貴博, 座間味義人, 小山敏広, 武智研志, 今西正樹, 堀ノ内裕也, 石澤有紀, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : ドラッグリポジショニングを切り口とした心肺蘇生後症候群治療薬の探索研究, 第27回日本医療薬学会年会, 2017年11月.
44.	座間味義人, 小山敏広, 石澤有紀, 新村貴博, 今西正樹, 武智研志, 堀ノ内裕也, 桐野靖, 中村敏己, 寺岡和彦, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 大規模医療情報を活用して心肺停止患者の生存率向上を志向したドラッグリポジショニング研究, 第27回日本医療薬学会年会, 2017年11月.
45.	三井茉綸, 座間味義人, 石澤有紀, 新村貴博, 武智研志, 今西正樹, 福島圭穣, 堀ノ内裕也, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 有害事象自発報告データベースを基にしたベバシズマブと相互作用を起こす薬剤の探索研究, 第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月.
46.	新村貴博, 座間味義人, 石澤有紀, 今西正樹, 武智研志, 福島圭穣, 堀ノ内裕也, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 心肺停止患者の予後に与えるニコランジルの影響-大規模レセプト情報を用いた検討, 第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月.
47.	漆崎汐里, 座間味義人, 石澤有紀, 新村貴博, 武智研志, 今西正樹, 福島圭穣, 堀ノ内裕也, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 大規模医療情報を活用して新規心肺蘇生後症候群治療薬の開発を志向したドラッグリポジショニング研究, 第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月.
48.	鍵本優有, 石澤有紀, 細岡真由子, 斎藤尚子, 鈴木琴子, 今西正樹, 堀ノ内裕也, 座間味義人, 武智研志, 池田康将, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 急性大動脈解離易発症マウスにおけるquercetinの効果, 第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月.
49.	田中恭平, 今西正樹, 近藤正輝, 生藤来希, 村井陽一, 座間味義人, 武智研志, 堀ノ内裕也, 石澤有紀, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : フェブキソスタットの尿酸合成抑制剤作用とは独立した血管線維化抑制作用の検討, 第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月.
50.	渡邊大晃, 池田康将, 濱野裕章, 堀ノ内裕也, 石澤有紀, 今西正樹, 座間味義人, 武智研志, 宮本理人, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 肥満・糖尿病におけるマクロファージ鉄の役割の検討, 第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月.
51.	濱野裕章, 池田康将, 渡邉大晃, 堀ノ内裕也, 石澤有紀, 今西正樹, 座間味義人, 武智研志, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 慢性腎臓病における尿毒素蓄積によるヘプシジン制御と鉄代謝破綻のメカニズムの解明, 第41回日本鉄バイオサイエンス学会学術集会, 2017年9月.
52.	池田康将, 堀ノ内裕也, 濱野裕章, 平山祐, 岸誠司, 石澤有紀, 今西正樹, 座間味義人, 武智研志, 宮本理人, 石澤啓介, 粟飯原賢一, 永澤秀子, 土屋浩一郎, 玉置俊晃 : 鉄摂取制限による尿細管間質障害の抑制効果の検討, 第41回日本鉄バイオサイエンス学会学術集会, 2017年9月.
53.	宮本理人, 梅本果奈, 上島沙弥香, 友成奈央実, 池田康将, 玉置俊晃, 土屋浩一郎 : 食後のエネルギー代謝調節を担うAMPK活性制御機構, 次世代を担う創薬医療薬理シンポジウム2017, 2017年8月.
54.	濱野裕章, 池田康将, 渡邊大晃, 堀ノ内裕也, 石澤有紀, 今西正樹, 座間味義人, 武智研志, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 慢性腎不全における尿毒素蓄積はヘプシジンを介した鉄代謝恒常性破綻に関与する, 大阪市大フォーラム, 2017年8月.
55.	新村貴博, 座間味義人, 石澤有紀, 今西正樹, 武智研志, 福島圭穣, 堀ノ内裕也, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 心肺蘇生後症候群治療薬の開発を目的としたドラッグリポジショニング研究-大規模医療情報を活用した検討-, 第255回徳島医学会学術集会, 2017年8月.
56.	座間味義人, 石澤有紀, 桐野靖, 三井茉綸, 漆崎汐里, 武智研志, 今西正樹, 堀ノ内裕也, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 有害事象自発報告データベースを切り口としたベバシズマブの抗腫瘍効果を減弱させる薬剤の探索研究, 医療薬学フォーラム2017 第25回クリニカルファーマシーシンポジウム, 2017年7月.
57.	堀ノ内裕也, 池田康将, 今西正樹, 座間味義人, 石澤有紀, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 経口FXa阻害剤の腎線維化抑制効果, 医療薬学フォーラム2017 第25回クリニカルファーマシーシンポジウム, 2017年7月.
58.	堀ノ内裕也, 池田康将, 石澤有紀, 今西正樹, 座間味義人, 武智研志, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 第Xa因子阻害剤は腎間質線維化を抑制する, 第131回日本薬理学会近畿部会, 2017年6月.
59.	濱野裕章, 池田康将, 渡邊大晃, 堀ノ内裕也, 石澤有紀, 今西正樹, 座間味義人, 武智研志, 石澤啓介, 土屋浩一郎, 玉置俊晃 : インドキシル硫酸蓄積はヘプシジン制御を介して鉄代謝恒常性破綻に関与する, 第131回日本薬理学会近畿部会, 2017年6月.
60.	池田康将, 堀ノ内裕也, 石澤有紀, 玉置俊晃 : 鉄摂取制限はタンパク過剰負荷による尿細管間質障害を軽減する, 第60回日本腎臓学会学術総会, 2017年5月.
61.	濱野裕章, 池田康将, 渡邉大晃, 堀ノ内裕也, 石澤有紀, 石澤啓介, 土屋浩一郎, 玉置俊晃 : インドキシル硫酸はヘプシジンを介した鉄代謝異常に関与する, 第60回日本腎臓学会学術総会, 2017年5月.
62.	堀ノ内裕也, 池田康将, 石澤有紀, 石澤啓介, 土屋浩一郎, 玉置俊晃 : FXa阻害剤は腎間質線維化を抑制する, 第60回日本腎臓学会学術総会, 2017年5月.
63.	Licht Miyamoto, Aihara Haruna, Xu Wenting, Jin Meina, Tomida Yosuke, Yamaoka Tomomi, Tanaka Naonobu, Yasumasa Ikeda, Toshiaki Tamaki, Yoshiki Kashiwada and Koichiro Tsuchiya : A limonene-derivative purified from Sudachi peel upregulates sirt1 and improves lipid /glucose metabolism in HFD-fed mice., 第60回日本糖尿病学会, May 2017.
64.	三井茉綸, 座間味義人, 石澤有紀, 漆崎汐里, 桐野靖, 斉家和仁, 森口浩史, 武智研志, 今西正樹, 堀ノ内裕也, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 有害事象自発報告データベースを基にしたベバシズマブの抗腫瘍効果を減弱させる薬剤の探索研究, 日本薬学会第137年会, 2017年3月.
65.	堀ノ内裕也, 池田康将, 石澤有紀, 石澤啓介, 土屋浩一郎, 玉置俊晃 : FXa 阻害剤の片側尿管結紮モデルマウスにおける腎間質線維化抑制作用, 日本薬学会第137年会, 2017年3月.
66.	生藤来希, 今西正樹, 田中恭平, 座間味義人, 武智研志, 堀ノ内裕也, 石澤有紀, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : アンジオテンシンII 誘発性血管リモデリングに対するキサンチンオキシダーゼ阻害剤の影響, 日本薬学会第137年会, 2017年3月.
67.	Yasumasa Ikeda and Toshiaki Tamaki : Excess iron on the risk of tissue injury, 第90回日本薬理学会年会, Mar. 2017.
68.	Yasumasa Ikeda and Toshiaki Tamaki : Excess iron action on risk of tissue injury, 第90回日本薬理学会年会年会企画ナノシンポジウム「機能性食品における薬理学」, Mar. 2017.
69.	堀ノ内裕也, 池田康将, 石澤有紀, 石澤啓介, 土屋浩一郎, 玉置俊晃 : Xa因子阻害薬は一側尿管結紮誘導性腎線維化を抑制する, 第90回日本薬理学会年会, 2017年3月.
70.	今西正樹, 田中恭平, 生藤来希, 座間味義人, 武智研志, 堀ノ内裕也, 石澤有紀, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : フェブキソスタットはアンジオテンシンII誘発性大動脈線維化を抑制する, 第90回日本薬理学会年会, 2017年3月.
71.	Masaki Imanishi, 田中恭平, 生藤来希, Yoshito Zamami, Kenshi Takechi, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yasumasa Ikeda, Hiromichi Fujino, Koichiro Tsuchiya, Toshiaki Tamaki and Keisuke Ishizawa : フェブキソスタットはアンジオテンシンII誘発性大動脈繊維化を抑制する, 第90回日本薬理学会年会(長崎), Mar. 2017.
72.	石澤有紀, 細岡真由子, 齊藤尚子, 今西正樹, 堀ノ内裕也, 座間味義人, 武智研志, 池田康将, 土屋浩一郎, 石澤啓介, 玉置俊晃 : ケルセチンの内皮保護作用を介したマウス大動脈解離発症に対する効果, 第90回日本薬理学会年会, 2017年3月.
73.	宮本理人, 友川剛己, 松田裕樹, 山根萌, 服部真奈, 大西怜奈, 池田康将, 玉置俊晃, 土屋浩一郎 : 身体運動時に生じる骨格筋代謝状態の変化における，中枢性調節機構の意義, 第90回日本薬理学会年会, 2017年3月.
74.	土屋浩一郎, 池田康将, 石澤有紀, 堀ノ内裕也, 宮本理人, 玉置俊晃 : 鉄ストレスと代謝性疾患-鉄ストレスによる疾患と，鉄ストレスによる治療, 日本薬学会第137年会, 2017年3月.
75.	座間味義人, 石澤有紀, 桐野靖, 三井茉綸, 漆崎汐里, 斉家和仁, 森口浩史, 武智研志, 今西正樹, 堀ノ内裕也, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 有害事象自発報告データベースを切り口としたベバシズマブと相互作用を起こす薬剤の探索研究, 第46回日本心脈管作動物質学会年会, 2017年2月.
76.	今西正樹, 田中恭平, 生藤来希, 座間味義人, 武智研志, 堀ノ内裕也, 石澤有紀, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : Angiotensin II誘発性血管リモデリングに対するfebuxostatの効果, 第46回日本心脈管作動物質学会, 2017年2月.
77.	宮本理人, 友川剛己, 松田裕樹, 山根萌, 服部真奈, 大西伶奈, 池田康将, 玉置俊晃, 土屋浩一郎, 土屋浩一郎 : 身体運動時に生じる骨格筋代謝状態の変化における，中枢を介した調節機構の意義, 第46回日本心脈管作動物質学会, 2017年2月.
78.	濱野裕章, 池田康将, 渡邉大晃, 堀ノ内裕也, 佐藤明穂, 大島啓亮, 石澤有紀, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 慢性腎不全における尿毒素蓄積が生体内鉄代謝に与える影響の検討, 第46回日本心脈管作動物質学会, 2017年2月.
79.	石澤有紀, 細岡真由子, 斎藤尚子, 鍵本優有, 今西正樹, 座間味義人, 堀ノ内裕也, 池田康将, 土屋浩一郎, 玉置俊晃, 石澤啓介 : ケルセチンによるマウス大動脈解離発症予防効果の検討, 第46回日本心脈管作動物質学会年会, 2017年2月.
80.	友川剛己, 宮本理人, 松田裕樹, 山根萌, 服部真奈, 大西怜奈, 池田康将, 玉置俊晃, 土屋浩一郎 : 水泳運動負荷時に生じる骨格筋AMPK活性化の新たなメカニズム，第46回日本心脈管作動物質学会年会, 2017年2月.
81.	寒川裕未, 福榮千花, 津田勝範, 宮本理人, 土屋浩一郎, 池田康将, 玉置俊晃, 濱野修一 : Artesunateによる細胞傷害発現機序の解明1, 第40回徳島県医学検査学会, 2016年12月.
82.	福榮千花, 寒川裕未, 津田勝範, 宮本理人, 土屋浩一郎, 池田康将, 玉置俊晃, 濱野修一 : Artesunateによる細胞傷害発現機序の解明2, 第40回徳島県医学検査学会, 2016年12月.
83.	今西正樹, 松永慎司, 石澤啓介, 玉置俊晃, 冨田修平 : 大動脈瘤形成における平滑筋由来HIF-1αの役割, 第26回日本循環薬理学会, 2016年12月.
84.	石澤有紀, 福永豊, 西良恵理子, 今西正樹, 堀ノ内裕也, 池田康将, 座間味義人, 武智研志, 石澤啓介, 土屋浩一郎, 橋本一郎, 玉置俊晃 : ニトロソニフェジピンは虚血性皮弁モデルにおいて皮弁壊死を抑制する, 第26回日本循環薬理学会, 2016年12月.
85.	木平孝高, 岸渕麗奈, 山口邦久, 藤村よしの, 佐藤英治, 玉置俊晃, 冨田修平 : 腎虚血再灌流障害におけるグルタチオン分解酵素 CHAC1 の役割, 第130回日本薬理学会近畿部会, 2016年11月.
86.	高橋梨恵, 宮本理人, 友川剛己, 宮武由実子, 阪上浩, 池田康将, 玉置俊晃, 土屋浩一郎 : 脳内グリコーゲンによる代謝調節効果の検討, 第130回日本薬理学会近畿部会, 2016年11月.
87.	福田恵介, 宮本理人, 高橋梨恵, 玉置俊晃, 池田康将, 土屋浩一郎 : スダチ果皮芳香成分が糖脂質代謝に与える影響, 第130回日本薬理学会近畿部会, 2016年11月.
88.	細岡真由子, 石澤有紀, 斎藤尚子, 今西正樹, 座間味義人, 宮本理人, 堀ノ内裕也, 池田康将, 石澤啓介, 玉置俊晃, 土屋浩一郎 : Quercetin による血管内皮細胞保護効果の検討, 第130回日本薬理学会近畿部会, 2016年11月.
89.	佐藤明穂, 池田康将, 濱野裕章, 堀ノ内裕也, 今尾瑞季, 渡邊大晃, 石澤有紀, 宮本理人, 石澤啓介, 玉置俊晃, 土屋浩一郎 : 鉄欠乏が骨格筋に与える作用の検討, 第55回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2016年11月.
90.	福永豊, 石澤有紀, 堀ノ内裕也, 池田康将, 石澤啓介, 土屋浩一郎, 玉置俊晃, 橋本一郎 : 虚血性皮弁壊死モデルにおける抗酸化薬ニトロソニフェジピンの壊死抑制効果, 第25回日本形成外科学会基礎学術集会, 2016年9月.
91.	三井茉綸, 座間味義人, 漆崎汐里, 斉家和仁, 森口浩史, 武智研志, 今西正樹, 堀ノ内裕也, 宮本理人, 石澤有紀, 池田康将, 藤野裕道, 土屋浩一郎, 玉置俊晃, 石澤啓介 : ドラッグリポジショニングを切り口としたベバシズマブ誘発高血圧に対する予防薬の探索研究, 第27回霧島神経薬理フォーラム(福岡), 2016年8月.
92.	今西正樹, 石澤有紀, 座間味義人, 田淵正樹, 玉置俊晃, 石澤啓介 : 脳卒中後の神経症状増悪に対するニトロソニフェジピンの効果, 第46回日本神経精神薬理学会年会( ソウル), 2016年7月.
93.	宮本理人, 秦野彩, 竹之熊和也, 土橋有希, 矢野友章, 池田康将, 玉置俊晃, 土屋浩一郎 : 速効型インスリン分泌促進薬とSGLT2阻害薬の併用による薬効の検討, 第129回日本薬理学会近畿部会, 2016年6月.
94.	石澤有紀, 細岡真由子, 斎藤尚子, 堀ノ内裕也, 今西正樹, 座間味義人, 池田康将, 石澤啓介, 土屋浩一郎, 玉置俊晃 : ケルセチン代謝産物Q3GAの血管内皮膚細胞に対する短期及び長期効果の検討, 第129回日薬理学会学会近畿部会( 広島), 2016年6月.
95.	池田康将, 佐藤明穂, 堀ノ内裕也, 石澤有紀, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 骨格筋分化における鉄の役割, 第129回日薬理学会学会近畿部会 (広島), 2016年6月.
96.	池田康将, 大島啓亮, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 鉄は低酸素誘導因子を抑制してエリスロポエチン発現を低下させる, 第59回日本腎臓学会学術総会, 2016年6月.
97.	宮本理人, 粟飯原遥菜, 許文婷, 靳美娜, 冨田洋輔, 山岡朋美, 田中直伸, 池田康将, 玉置俊晃, 柏田良樹, 土屋浩一郎 : スダチ果皮における抗メタボリックシンドローム作用を有する物質の同定, 日本薬学会第136年会(横浜), 2016年3月.
98.	細岡真由子, 石澤有紀, 斎藤尚子, 宮本理人, 今西正樹, 座間味義人, 木平孝高, 池田康将, 石澤啓介, 玉置俊晃, 土屋浩一郎 : ケルセチン生体内代謝産物 quercetin -3-O-β-Dglucuronideによる血管内皮細胞保護効果, 日本薬学会第136年会(横浜), 2016年3月.
99.	鍵本優有, 石澤有紀, 今西正樹, 座間味義人, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 無機リン刺激による血管平滑筋細胞石灰化におけるrho-kinase 及び cyclophilinA の関与, 日本薬学会第136年会(横浜), 2016年3月.
100.	渡邉大晃, 池田康将, 濱野裕章, 佐藤明穂, 堀ノ内裕也, 石澤有紀, 木平孝高, 宮本理人, 土屋浩一郎, 玉置俊晃, 石澤啓介 : 慢性腎臓病におけるヘプシジン制御メカニズムの検討, 日本薬学会第136年会(横浜), 2016年3月.
101.	佐藤明穂, 池田康将, 堀ノ内裕也, 濱野裕章, 今尾瑞季, 渡邉大晃, 石澤有紀, 木平孝高, 石澤啓介, 玉置俊晃, 宮本理人, 土屋浩一郎 : 鉄過剰による骨格筋分化抑制作用の解明, 日本薬学会第136年会(横浜), 2016年3月.
102.	Yasumasa Ikeda, Keisuke Oshima, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki : Iron Supplementation Suppressed Erythropoietin Expression through HIF-dependent Pathway, The 80th Annual Scientific Meeting of the Japanese Circulation Society, Mar. 2016.
103.	太田和馬, 木平孝高, 岸渕麗奈, 石澤有紀, 池田康将, 石澤啓介, 土屋浩一郎, 冨田修平, 玉置俊晃 : 電位依存性カリウムチャネルKv2.2は腎虚血再灌流障害の軽減に関与する, 第89回日本薬理学会年会(神奈川), 2016年3月.
104.	岸渕麗奈, 木平孝高, 山口邦久, 石澤有紀, 池田康将, 石澤啓介, 冨田修平, 土屋浩一郎, 玉置俊晃 : HIF-1aはアポトーシス制御因子Bcl-2及びCHAC1の発現制御を介して腎虚血再灌流障害からの回復に関与する, 第89回日本薬理学会年会(神奈川), 2016年3月.
105.	斎藤尚子, 石澤有紀, 細岡真由子, 木平孝高, 今西正樹, 座間味義人, 池田康将, 石澤啓介, 土屋浩一郎, 玉置俊晃 : ケルセチン代謝物Q3GAによる血管内皮細胞保護効果の検討, 第89回日本薬理学会年会(神奈川), 2016年3月.
106.	青木友里, 石澤有紀, 高田真衣, 田渕正樹, 今西正樹, 座間味義人, 福永豊, 木平孝高, 池田康将, 土屋浩一郎, 石澤啓介, 玉置俊晃 : 神経突起伸長および脳卒中後神経症状に対するニトロソニフェジピンの効果, 第89回日本薬理学会年会(神奈川), 2016年3月.
107.	大島啓亮, 池田康将, 堀ノ内裕也, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 鉄のエリスロポエチン発現への影響の検討, 第89回日本薬理学会年会(神奈川), 2016年3月.
108.	佐藤明穂, 池田康将, 堀ノ内裕也, 濱野裕章, 今尾瑞季, 渡邉大晃, 石澤有紀, 木平孝高, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 鉄欠乏に伴う骨格筋萎縮メカニズム, 第89回日本薬理学会年会(神奈川), 2016年3月.
109.	Licht Miyamoto, Haruna Aihara, Wenting Xu, Meina Jin, Yosuke Tomida, Tomomi Yamaoka, Naonobu Tanaka, Yasumasa Ikeda, Toshiaki Tamaki, Yoshiki Kashiwada and Koichiro Tsuchiya : Identification of an active compound on lipid metabolism from Sudachi peel, 薬理学会(パシフィコ), Mar. 2016.
110.	宮本理人, 粟飯原遥菜, Xu Wenting, Jin Meina, 冨田洋輔, 山岡朋美, 田中直伸, 池田康将, 玉置俊晃, 柏田良樹, 土屋浩一郎 : 脂質低下作用を有するスダチ果皮由来化合物の薬理作用, 第89回日本薬理学会年会(神奈川), 2016年3月.
111.	濱野裕章, 池田康将, 渡邉大晃, 佐藤明穂, 大島啓亮, 堀ノ内裕也, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 尿毒素は慢性腎不全におけるヘプシジン発現に関与する, 第89回日本薬理学会年会(神奈川), 2016年3月.
112.	今西正樹, 井口道代, 冨田紀子, 松永慎司, 玉置俊晃, 冨田修平 : Hypoxia-inducible factor-1 in smooth muscle cells protects against aortic aneurysm formation via elastin-fiber formation, 第89回日本薬理学会年会(神奈川), 2016年3月.
113.	Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshitaka Kihira, Licht Miyamoto, Yoshito Zamami, Yasumasa Ikeda, Koichiro Tsuchiya, Toshiaki Tamaki and Keisuke Ishizawa : Development of endothelial dysfunction-induced aortic dissection model and search for a preventive strategy, 第89回日本薬理学会年会(神奈川), Mar. 2016.
114.	今西正樹, 石澤啓介, 小原佑介, 櫻田巧, 戸谷紘基, 長尾朋子, 壱岐豊, 細岡真由子, 石澤有紀, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : ニフェジピン光分解産物による血管リモデリング抑制効果, 第252回徳島医学会学術集会(平成27年度冬期), 2016年2月.
115.	今西正樹, 井口道代, 冨田紀子, 松永慎司, 玉置俊晃, 冨田修平 : 平滑筋由来HIF-1 αによる弾性繊維構築を介した大動脈瘤形成抑制メカニズムの検討, 第45回日本心脈管作動物質学会, 2016年2月.
116.	大島啓亮, 池田康将, 堀ノ内裕也, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 鉄のエリスロポエチン発現への影響の検討, 第45回日本心脈管作動物質学会, 2016年2月.
117.	今西正樹, 石澤啓介, 小原佑介, 櫻田巧, 戸谷紘基, 長尾朋子, 壱岐豊, 細岡真由子, 石澤有紀, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : ニトロソニフェジピンによる抗大動脈瘤機序の検討, 第45回日本心脈管作動物質学会, 2016年2月.
118.	石澤有紀, 石澤啓介, 鍵本優有, 斎藤尚子, 高田真衣, 木平孝高, 今西正樹, 池田康将, 土屋浩一郎, 玉置俊晃 : 高リン刺激は血管平滑筋細胞においてrho-kinase-cyclophilin A経路を活性化させる, 第45回日本心脈管作動物質学会, 2016年2月.
119.	繁冨明日香, 宮本理人, 土屋浩一郎, 玉置俊晃, 濱野修一 : LED灯によるビリルビン光分解の検討, 徳島検査医学会, 2015年12月.
120.	池田康将, 玉置俊晃 : 臓器障害における生体内鉄代謝の意義と鉄除去による病態改善効果, 心血管代謝週間(CVMW)(第19回日本心血管内分泌代謝学会学術総会) シンポジウム, 2015年12月.
121.	池田康将, 濱野裕章, 渡邉大晃, 堀ノ内裕也, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 慢性腎臓病におけるヘプシジン制御メカニズムの検討, 第25回日本循環薬理学会, 2015年12月.
122.	石澤有紀, 石澤啓介, 高田真衣, 田渕正樹, 今西正樹, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : ニトロソニフェジピンは悪性脳卒中易発性高血圧自然発症ラットの生命予後を改善する, 第25回日本循環薬理学会, 2015年12月.
123.	斎藤尚子, 石澤有紀, 石澤啓介, 戸谷紘基, 今西正樹, 鍵本優有, 細岡真由子, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : 大動脈解離発症における内皮障害の関与, 第25回日本循環薬理学会, 2015年12月.
124.	濱野裕章, 池田康将, 堀ノ内裕也, 佐藤明穂, 渡邉大晃, 大島啓亮, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 慢性腎不全における尿毒素によるヘプシジン制御機構, 第128回日本薬理学会近畿部会, 2015年11月.
125.	今尾瑞季, 池田康将, 佐藤明穂, 濱野裕章, 堀ノ内裕也, 宮本理人, 木平孝高, 石澤有紀, 石澤啓介, 玉置俊晃, 土屋浩一郎 : 鉄蓄積によって引き起こされる骨格筋萎縮のメカニズム, 第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2015年11月.
126.	高田真衣, 石澤啓介, 田渕正樹, 石澤有紀, 宮本理人, 木平孝高, 池田康将, 玉置俊晃, 土屋浩一郎 : 悪性脳卒中易発性高血圧自然発症ラットの神経症状に対するニトロソニフェジピンの効果, 第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2015年11月.
127.	戸谷紘基, 石澤啓介, 石澤有紀, 細岡真由子, 鍵本優有, 斎藤尚子, 宮本理人, 木平孝高, 池田康将, 玉置俊晃, 土屋浩一郎 : 大動脈解離発症における内皮障害の関与の検討, 第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2015年11月.
128.	池田康将, 佐藤明穂, 堀ノ内裕也, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 鉄欠乏は骨格筋量減少の原因となる, 第39回日本鉄バイオサイエンス学会学術集会, 2015年8月.
129.	Ariunzaya Burentogtokh, 木平孝高, 石澤有紀, 池田康将, 土屋浩一郎, 玉置俊晃 : YC1 increased adiponectin expression in 3T3-L1 adipocytes, 次世代を担う創薬・医療薬理シンポジウム2015, 2015年8月.
130.	石澤有紀, 石澤啓介, 大越瑞穂, 土肥紗希子, 木平孝高, 池田康将, 玉置俊晃 : 血管石灰化シグナルにおけるRhoキナーゼおよびサイクロフィリンAの関与, 第47回日本動脈硬化学会総会・学術集会, 2015年7月.
131.	池田康将, 粟飯原賢一, 吉田守美子, 赤池雅史, 玉置俊晃, 松本俊夫 : 心血管疾患における男性ホルモンの意義, 第15回日本抗加齢医学会総会シンポジウム「知って得するテストステロンアップデート」, 2015年5月.
132.	池田康将, Kanai Yusuke, 堀ノ内裕也, 石澤有紀, 木平孝高, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃 : Bilirubin Promotes Ischemic-Induced Revascularization through Akt-eNOS Pathway, 第79回日本循環器学会学術集会, 2015年4月.
133.	木平孝高, 岸渕麗奈, 山口邦久, 石澤有紀, 池田康将, 石澤啓介, 冨田修平, 土屋浩一郎, 玉置俊晃 : 腎虚血再灌流障害において低酸素誘導因子が制御する因子の探索, 日本薬学会第135年会(神戸), 2015年3月.
134.	高田真衣, 石澤啓介, 田渕正樹, 石澤有紀, 木平孝高, 池田康将, 玉置俊晃, 土屋浩一郎 : 悪性脳卒中易発性高血圧自然発症ラットに対するニトロソニフェジピンの効果, 日本薬学会第135年会(神戸), 2015年3月.
135.	池田康将, 堀ノ内裕也, 石澤有紀, 木平孝高, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃 : ビリルビンは虚血後血管新生を促進する, 第88回日本薬理学会年会(愛知), 2015年3月.
136.	石澤有紀, 石澤啓介, 田渕正樹, 高田真衣, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : ニトロソニフェジピンは悪性脳卒中易発性高血圧自然発症ラットの生存期間を延長させる, 第88回日本薬理学会年会(愛知), 2015年3月.
137.	戸谷紘基, 石澤啓介, 石澤有紀, 小原佑介, 長尾朋子, 今西正樹, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : 大動脈解離発症における血管内皮機能障害の関与, 第88回日本薬理学会年会(愛知), 2015年3月.
138.	岸渕麗奈, 木平孝高, 山口邦久, 石澤有紀, 石澤啓介, 池田康将, 冨田修平, 土屋浩一郎, 玉置俊晃 : 低酸素誘導因子-1αは腎虚血再灌流障害においてアボトーシスの誘導に関与する, 第88回日本薬理学会年会(愛知), 2015年3月.
139.	今西正樹, 井口道代, 冨田紀子, ツナピパナギオタ, 松永慎司, 石澤啓介, 玉置俊晃, 冨田修平 : 血管リモデリングにおける平滑筋由来hypoxia-inducible factor-1αの役割, 第88回日本薬理学会年会(愛知), 2015年3月.
140.	Mizuho Ogoshi, Yuki Izawa-Ishizawa, Sakiko Doi, Keisuke Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : 血管平滑筋細胞において無機リンによる石灰化シグナルにはRho-kinaseおよびcyclophilin Aが関与する, 第88回日本薬理学会年会(愛知), Mar. 2015.
141.	Burentogtokh Ariunzaya, Yoshitaka Kihira, Yuki Izawa-Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : Hypoxia decreases glucagon-like peptide-1 secretion from glutag cell lines, 第88回日本薬理学会年会(愛知), Mar. 2015.
142.	池田康将, 金井佑亮, 堀ノ内裕也, 石澤有紀, 木平孝高, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃 : ビリルビンの血管新生促進作用の検討, 第44回日本心脈管作動物質学会, 2015年2月.
143.	森本悠里, 宮本理人, 土屋浩一郎, 玉置俊晃, 濱野修一 : セスキテルペンラクトン誘導体の鉄依存細胞障害機構の解明, 第38回徳島県医学検査学会, 2014年12月.
144.	池田康将, 金井佑亮, 堀ノ内裕也, 石澤有紀, 木平孝高, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃 : ビリルビンは血管内皮細胞を活性化させて，虚血後血管新生を促進する, 第24回循環薬理学会, 2014年12月.
145.	石澤有紀, 石澤啓介, 長尾朋子, 戸谷紘基, 小原佑介, 細岡真由子, 高田真衣, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : 新規薬剤誘発性大動脈解離モデルを用いたスタチンの効果の検討, 第24回循環薬理学会, 2014年12月.
146.	今西正樹, 村上正樹, 前田悠作, 冨田紀子, Tsounapi Panagiota, 松永慎司, 玉置俊晃, 冨田修平 : 血管傷害モデルに伴う血管リモデリング形成に対する骨髄由来細胞のHIF-1αの関与, 第67回日本薬理学会西南部会, 2014年11月.
147.	今西正樹, 井口道代, 冨田紀子, Tsounapi Panagiota, 松永慎司, 玉置俊晃, 冨田修平 : 血管リモデリングにおける平滑筋由来HIF-1αの作用, 第12回がんとハイポキシア研究会, 2014年11月.
148.	今西正樹, 井口道代, 冨田紀子, Tsounapi Panagiota, 松永慎司, 玉置俊晃, 冨田修平 : 血管リモデリングにおける平滑筋由来HIF-1αの作用, 第12回がんとハイポキシア研究会, 2014年11月.
149.	岸渕麗奈, 木平孝高, 山口邦久, 石澤有紀, 池田康将, 冨田修平, 土屋浩一郎, 玉置俊晃 : 低酸素誘導因子の機能不全は腎虚血再灌流障害からの回復を阻害する, 第36回生体膜と薬物の相互作用シンポジウム, 2014年11月.
150.	木平孝高, 石澤有紀, 池田康将, 土屋浩一郎, 玉置俊晃, 冨田修平 : 高脂肪食誘発肥満に対する脂肪特異的低酸素誘導因子欠損の影響, 第36回生体膜と薬物の相互作用シンポジウム, 2014年11月.
151.	長尾朋子, 石澤啓介, 戸谷紘基, 小原佑介, 今西正樹, 石澤有紀, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : HMG-CoA 還元酵素阻害薬の大動脈解離に対する効果, 第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月.
152.	山根萌, 宮本理人, 冨田洋輔, 竹之熊和也, 川崎彩, 山岡朋美, 石澤啓介, 玉置俊晃, 土屋浩一郎 : ヒト腎糸球体内皮細胞における亜硝酸塩によるAMPK-eNOS活性化経路の検討, 第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月.
153.	長尾朋子, 石澤啓介, 戸谷紘基, 小原佑介, 今西正樹, 石澤有紀, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : HMG-CoA 還元酵素阻害薬の大動脈解離に対する効果, 第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月.
154.	小原佑介, 石澤啓介, 櫻田巧, 戸谷紘基, 長尾朋子, 壱岐豊, 細岡真由子, 今西正樹, 石澤有紀, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : 大動脈瘤形成に対する新規抗酸化薬の効果, 第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月.
155.	山根萌, 宮本理人, 冨田洋輔, 竹之熊和也, 川崎彩, 山岡朋美, 石澤啓介, 玉置俊晃, 土屋浩一郎 : 亜硝酸塩による AMPK-eNOS 経路活性化, 第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月.
156.	岸渕麗奈, 木平孝高, 山口邦久, 石澤有紀, 池田康将, 冨田修平, 土屋浩一郎, 玉置俊晃 : 低酸素誘導因子の腎虚血再灌流障害に対する役割, 第126回日本薬理学会近畿部会, 2014年10月.
157.	長尾朋子, 石澤啓介, 戸谷紘基, 小原佑介, 今西正樹, 石澤有紀, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : 大動脈解離に対するピタバスタチンの効果, 第126回日本薬理学会近畿部会, 2014年10月.
158.	山根萌, 宮本理人, 冨田洋輔, 竹之熊和也, 石澤啓介, 玉置俊晃, 土屋浩一郎 : ヒト腎糸球体内皮細胞におけるAMPK-eNOS経路の活性化, 第126回日本薬理学会近畿部会, 2014年10月.
159.	池田康将, 今尾瑞季, 佐藤明穂, 堀ノ内裕也, 石澤有紀, 木平孝高, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 鉄による骨格筋萎縮メカニズムの検討, 日本鉄バイオサイエンス学会第38回学術集会, 2014年9月.
160.	小原佑介, 石澤啓介, 櫻田巧, 戸谷紘基, 長尾朋子, 壱岐豊, 細岡真由子, 石澤有紀, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : ニトロソニフェジピンは大動脈瘤の形成を抑制する, 次世代を担う創薬・医療薬理シンポジウム 2014, 2014年8月.
161.	戸谷紘基, 石澤啓介, 小原佑介, 長尾朋子, 石澤有紀, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : 血管内皮障害を介する新規大動脈解離モデルの作製, 次世代を担う創薬・医療薬理シンポジウム 2014, 2014年8月.
162.	山根萌, 宮本理人, 冨田洋輔, 竹之熊和也, 石澤啓介, 玉置俊晃, 土屋浩一郎 : 亜硝酸塩による AMPK-eNOS 経路活性化, 次世代を担う創薬・医療薬理シンポジウム 2014, 2014年8月.
163.	山根萌, 宮本理人, 冨田洋輔, 竹之熊和也, 石澤啓介, 玉置俊晃, 土屋浩一郎 : 亜硝酸塩によるAMPK-eNOS経路活性化, 生体機能と創薬シンポジウム 2014, 2014年8月.
164.	矢野友章, 宮本理人, 竹之熊和也, 福田恵介, 津田勝範, 石澤啓介, 木平孝高, 池田康将, 玉置俊晃, 土屋浩一郎 : 食事による血中NOレベル変動の検討, 第249回徳島医学会, 2014年7月.
165.	小原佑介, 石澤啓介, 櫻田巧, 戸谷紘基, 長尾朋子, 壱岐豊, 石澤有紀, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : 薬剤誘導性大動脈瘤モデルに対するニトロソニフェジピンの効果, 第125回日本薬理学会近畿部会, 2014年6月.
166.	池田康将, 田島壮一郎, 堀ノ内裕也, 石澤有紀, 木平孝高, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃 : アンジオテンシンIIは鉄吸収制御と生体内鉄分布変化に関与する, 第125回日本薬理学会近畿部会, 2014年6月.
167.	今西正樹, 冨田修平, 石澤啓介, 木平孝高, 石澤有紀, 池田康将, 山野範子, 土屋浩一郎, 玉置俊晃 : 血管リモデリングにおける低酸素誘導因子HIF-1αの役割, 日本薬学会第134年会, 2014年3月.
168.	木平孝高, Ariunzaya Burentogtokh, 伊藤麻里, 山野範子, 石澤有紀, 石澤啓介, 池田康将, 土屋浩一郎, 玉置俊晃 : 腸管L細胞のグルカゴン様ペプチド-1分泌に対する低酸素の影響, 日本薬学会第134年会, 2014年3月.
169.	石澤啓介, 石澤有紀, 山野範子, 布あさ美, 今西正樹, 櫻田巧, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : ニトロソニフェジピンはeNOS非依存的に内皮障害を伴う腎障害の進展を抑制する, 第87回日本薬理学会年会, 2014年3月.
170.	宮本理人, 山根萌, 冨田洋輔, 竹之熊和也, 石澤啓介, 玉置俊晃, 土屋浩一郎 : 亜硝酸塩による腎保護作用および糖脂質代謝改善作用におけるAMPKの意義, 第87回日本薬理学会年会, 2014年3月.
171.	今尾瑞季, 池田康将, 堀ノ内裕也, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 鉄によって引き起こされる骨格筋萎縮のメカニズム, 第87回日本薬理学会年会, 2014年3月.
172.	堀ノ内裕也, Summers A. Fiona, Ehrenshaft Marilyn, 土屋浩一郎, 玉置俊晃, Mason P. Ronald : Investigating free radical generation in HepG2 cells induced by aromatic amine compounds using immuno-spin trapping, 第87回日本薬理学会年会, 2014年3月.
173.	石澤有紀, Le Nhat-Tu, 竹井雄一郎, Heo Kyung-Sun, Lee Hakjoo, Smrcka Alan, Miller Benjamin, Ko Kyung-Ae, Ture Sara, Morrell Craig, 藤原敬己, 赤池雅史, 玉置俊晃, 阿部純一 : 内皮細胞におけるERK5活性化を介したスタチン・抗マラリア薬の抗炎症作用の検討, 第87回日本薬理学会年会, 2014年3月.
174.	井口道代, 冨田紀子, 今西正樹, 黒部裕嗣, 菅澤典子, 佐藤至, 松永慎司, 玉置俊晃, 冨田修平 : 肺高血圧症モデルマウスにおける平滑筋細胞での低酸素応答転写因子の役割, 第87回日本薬理学会年会, 2014年3月.
175.	池田康将, 田島壮一郎, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 玉置俊晃 : アンジオテンシンIIは十二指腸鉄輸送体発現とマクロファージ鉄量を増加させる, 第43回日本心脈管作動物質学会, 2014年2月.
176.	山脇早穂, 佐藤佑太, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃, 濱野修一 : リチウム定量にあたえる共存物質の影響, 第37回徳島県医学検査学会, 2013年12月.
177.	佐藤佑太, 山脇早穂, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃, 濱野修一 : セスキテルペンラクトン誘導体の鉄依存ラジカル生成過程の解明, 第37回徳島県医学検査学会, 2013年12月.
178.	今西正樹, 冨田修平, 黒部裕嗣, 石澤啓介, 木平孝高, 池田康将, 山野範子, 石澤有紀, 土屋浩一郎, 玉置俊晃 : 薬剤誘導性大動脈瘤モデルにおける平滑筋由来hypoxia-inducible factor-1αの役割, 第23回日本循環薬理学会, 2013年12月.
179.	森本篤志, 冨田修平, 木平孝高, 池田康将, 橋本一郎, 高久暢, 中西秀樹, 玉置俊晃 : 血管内皮細胞特異的HIF-2α強制発現マウスを用いた虚血皮弁モデルの作製と検討, 第22回日本形成外科学会基礎学術集会, 2013年11月.
180.	木平孝高, 冨田修平, 山野範子, 石澤有紀, 石澤啓介, 池田康将, 土屋浩一郎, 玉置俊晃 : 肥満に伴う脂肪組織炎症に対する低酸素誘導因子の役割, 第124回日本薬理学会近畿部会, 2013年11月.
181.	布あさ美, 石澤啓介, 山野範子, 石澤有紀, 櫻田巧, 今西正樹, 宮本理人, 木平孝高, 池田康将, 玉置俊晃, 土屋浩一郎 : ニトロソニフェジピンは血管内皮機能を改善することで糖尿病性腎症の進展を抑制する, 第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2013年10月.
182.	鈴木雄太, 今西正樹, 冨田修平, 石澤啓介, 木平孝高, 池田康将, 山野範子, 石澤有紀, 土屋浩一郎, 玉置俊晃 : 平滑筋由来HIF-1 αがアンジオテンシンII 誘発血管リモデリングに関与するメカニズム, 第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2013年10月.
183.	村上正樹, 前田悠作, 冨田修平, 今西正樹, 木平孝高, 石澤啓介, 山野範子, 石澤有紀, 池田康将, 土屋浩一郎, 玉置俊晃 : 血管傷害モデルに伴う血管リモデリングにおける骨髄由来細胞のHIF1 αの役割, 第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2013年10月.
184.	三宅真理子, 木平孝高, 冨田修平, 山野範子, 石澤有紀, 石澤啓介, 池田康将, 土屋浩一郎, 玉置俊晃 : 脂肪細胞の低酸素誘導因子欠損による耐糖能改善メカニズムの解析, 第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2013年10月.
185.	池田康将, 田島壮一郎, 今尾瑞季, 堀ノ内裕也, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 玉置俊晃 : フェリチンの炎症惹起作用, 第37回日本鉄バイオサイエンス学会, 2013年9月.
186.	村上正樹, 冨田修平, 前田悠作, 今西正樹, 山野範子, 石澤有紀, 木平孝高, 石澤啓介, 池田康将, 土屋浩一郎, 玉置俊晃 : 血管傷害モデルに伴う血管リモデリング形成過程には，傷害部位に動員される骨髄由来細胞のHIFが関与する, 次世代を担う創薬・医療薬理シンポジウム2013, 2013年8月.
187.	山野範子, 石澤啓介, 小堀浩幸, 漆原真樹, 石澤有紀, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : 糖尿病性腎症における腎内局所アンジオテンシノーゲンに対するニトロソニフェジピンの効果, 第123回日本薬理学会近畿部会, 2013年7月.
188.	今西正樹, 石澤啓介, 木平孝高, 池田康将, 山野範子, 石澤有紀, 土屋浩一郎, 玉置俊晃, 冨田修平 : 血管平滑筋細胞のhypoxia-inducible factor-1αがangiotensinⅡ誘発血管リモデリング形成に関与するメカニズムの解析, 第34回日本炎症・再生医学会, 2013年7月.
189.	堀ノ内裕也, Fiona A. SUMMERS, Marilyn EHRENSHAFT, 玉置俊晃, Ronald P. MASON : フリーラジカル直接検出法immuno-spin trapping, In-Cell Westernとconfocal microscopyを用いた環境汚染物質の細胞毒性評価, 第40回日本毒性学会学術年会, 2013年6月.
190.	石澤啓介, 山野範子, 石澤有紀, 櫻田巧, 今西正樹, 布あさ美, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : ニトロソニフェジピンは血管内皮保護作用を示して糖尿病性腎症進展を抑制する, 第56回日本腎臓学会学術総会, 2013年5月.
191.	今西正樹, 石澤啓介, 櫻田巧, 石澤有紀, 山野範子, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : 酸化ストレスに起因する心腎血管障害の克服を目指す新規治療薬開発, 日本薬学会第133年会, 2013年3月.
192.	土屋浩一郎, 池田康将, 田島壮一郎, 木平孝高, 石澤啓介, 石澤有紀, 宮本理人, 山野範子, 玉置俊晃 : 糖尿病に対する鉄の関与とキレート療法, 日本薬学会第133年会, 2013年3月.
193.	今西正樹, 冨田修平, 石澤啓介, 木平孝高, 池田康将, 山野範子, 石澤有紀, 土屋浩一郎, 玉置俊晃 : Hypoxia-inducible factor-1a; in vascular smooth muscle cells contributes to AT1 receptor expression in angiotensin II-induced vascular remodeling in mice, 第86回日本薬理学会年会, 2013年3月.
194.	伊藤麻里, 木平孝高, 山野範子, 石澤有紀, 石澤啓介, 池田康将, 土屋浩一郎, 冨田修平, 玉置俊晃 : Secretion of glucagon-like peptide-1 from Intestinal L cell in hypoxia, 第86回日本薬理学会年会, 2013年3月.
195.	田島壮一郎, 池田康将, 土屋浩一郎, 堀ノ内裕也, 櫻田巧, 木平孝高, 石澤有紀, 石澤啓介, 川添和義, 水口和生, 玉置俊晃 : The influence of angiotensin II on duodenal iron absorption, 第86回日本薬理学会年会, 2013年3月.
196.	池田康将, 田島壮一郎, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 玉置俊晃 : Bovine lactoferrin stimulated angiogenesis in response to ischemic hindlimb, 第86回日本薬理学会年会, 2013年3月.
197.	石澤有紀, 石澤啓介, 土肥紗希子, 今西正樹, 櫻田巧, 山野範子, 小原祐介, 長尾朋子, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : Y-27632, a rho-kinase inhibitor, inhibits inorganic phosphate-induced ERK1/2 phosphorylation and ALP activity in vascular smooth muscle cells, 第86回日本薬理学会年会, 2013年3月.
198.	大園伊織, 池田康将, 田島壮一郎, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 玉置俊晃 : The Effects of Iron chelatoion against Renal Fibrosis in Unilateral Ureteral Obstruction Mice Model, 第86回日本薬理学会年会, 2013年3月.
199.	保科耀司, 木平孝高, 冨田修平, 三宅真理子, 山野範子, 石澤有紀, 石澤啓介, 池田康将, 土屋浩一郎, 玉置俊晃 : Adipocyte-specific hypoxia-inducible factor-1alpha knockout stimulated GLP-1 and insulin secretions in mice, 第86回日本薬理学会年会, 2013年3月.
200.	Noriko Yamano, Keisuke Ishizawa, Shoko Fujii, Asami Nuno, Masaki Imanishi, Takumi Sakurada, Yuta Suzuki, Furi Endo, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : Effects of nitrosonifedipine on the diabetic nephropathy with the endothelial dysfunction, 第86回日本薬理学会年会, Mar. 2013.
201.	Yasumasa Ikeda, Hideaki Enomoto, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Low Iron Diet Limits Development of Diabetic Nephropathy In db/db Mice, 第77回日本循環器学会学術集会, Mar. 2013.
202.	T Nakayama, Hirotsugu Kurobe, H Sugasawa, Hajime Kinoshita, M Higashida, Y Matsuoka, Y Yoshida, Y Hirata, M Sakata, Yousuke Takahama, Masataka Sata, Toshiaki Tamaki, Tetsuya Kitagawa and Shuhei Tomita : Macrophage-specific HIF-1a-deficient Mice Suppress Vascular Remodeling., 第77回日本循環器学会学術集会, Mar. 2013.
203.	中山泰介, 冨田修平, 黒部裕嗣, 菅澤典子, 木下肇, 菅野幹雄, 神原保, 藤本鋭貴, 北市隆, 玉置俊晃, 佐田政隆, 北川哲也 : 小口径グラフト開存を目的とするマクロファージHIFと極性の動脈リモデリング基礎研究, 第43回日本心臓血管外科学会学術総会, 2013年2月.
204.	石澤有紀, 石澤啓介, 山野範子, 櫻田巧, 今西正樹, 藤井聖子, 布あさ美, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : ニトロソニフェジピンは血管内皮細胞障害を伴う糖尿病性腎症の進展を抑制する, 第42回日本心脈管作動物質学会, 2013年2月.
205.	田島壮一郎, 池田康将, 榎本英明, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 水口和生, 玉置俊晃 : 鉄制限食によってdb/dbマウスの糖尿病性腎症進展は抑制される, 第42回日本心脈管作動物質学会, 2013年2月.
206.	土肥紗希子, 石澤有紀, 石澤啓介, 櫻田巧, 今西正樹, 小原祐介, 長尾朋子, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : 無機リン刺激による血管平滑筋細胞石灰化におけるRho-kinaseの関与, 第42回日本心脈管作動物質学会, 2013年2月.
207.	木平孝高, 冨田修平, 三宅真理子, 保科耀司, 山野範子, 石澤有紀, 石澤啓介, 池田康将, 土屋浩一郎, 玉置俊晃 : 脂肪細胞特異的低酸素誘導因子欠損マウスに観察される耐糖能の改善にはglucagon-like peptide-1が関与する, 第42回日本心脈管作動物質学会, 2013年2月.
208.	冨田修平, 木平孝高, 今西正樹, 玉置俊晃 : 疾患に伴う血管リモデリング進展過程における低酸素応答性転写制御因子HIFの役割, 第85回日本生化学会大会, 2012年12月.
209.	石澤啓介, 今西正樹, 鈴木雄太, 木平孝高, 池田康将, 山野範子, 石澤有紀, 土屋浩一郎, 玉置俊晃, 冨田修平 : Angiotensin II慢性投与はhypoxia-inducible factor-1αを介して血管リモデリングを惹起する, 第33回日本臨床薬理学会学術総会, 2012年12月.
210.	今西正樹, 冨田修平, 石澤啓介, 木平孝高, 池田康将, 山野範子, 石澤有紀, 土屋浩一郎, 玉置俊晃 : 血管平滑筋細胞のhypoxia-inducible factor-1αがangiotensinⅡ誘発血管リモデリング形成に寄与するメカニズムの解析, 第22回日本循環薬理学会, 2012年11月.
211.	池田康将, 田島壮一郎, 石澤有紀, 木平孝高, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 鉄吸収機構におけるAngiotensinⅡの効果の検討, 第122回日本薬理学会近畿部会, 2012年11月.
212.	藤井聖子, 石澤啓介, 櫻田巧, 山野範子, 石澤有紀, 今西正樹, 布あさ美, 鈴木雄太, 木平孝高, 池田康将, 玉置俊晃, 土屋浩一郎 : Nifedipine 光分解産物であるnitrosonifedipine は糖尿病性腎症進展を抑制する, 第51回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2012年11月.
213.	中山泰介, 冨田修平, 黒部裕嗣, 菅澤典子, 木下肇, 菅野幹雄, 神原保, 藤本鋭貴, 北市隆, 玉置俊晃, 佐田政隆, 高浜洋介, 北川哲也 : 小口径グラフト開存性改善を目的とする血管リモデリングにおけるマクロファージの基礎研究, 第65回日本胸部外科学会定期学術集会, 2012年10月.
214.	今西正樹, 石澤啓介, 木平孝高, 池田康将, 山野範子, 石澤有紀, 土屋浩一郎, 冨田修平, 玉置俊晃 : 血管平滑筋細胞におけるHIF-1αのangiotensinⅡ誘発血管リモデリング形成およびAT1受容体発現への関与;平滑筋特異的HIF-1α遺伝子欠損マウスを用いた検討 The Role of HIF-1α in angiotensin Ⅱ-induced Vascular Remodeling and AT1 Receptor Expression in Vascular Smooth Muscle Cells, 第35回日本高血圧学会総会, 2012年9月.
215.	布あさ美, 石澤啓介, 藤井聖子, 櫻田巧, 山野範子, 石澤有紀, 今西正樹, 鈴木雄太, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃 : 糖尿病性腎症進展に対するニトロソニフェジピンの抑制作用, 次世代を担う創薬・医療薬理シンポジウム2012, 2012年9月.
216.	今西正樹, 石澤啓介, 木平孝高, 池田康将, 山野範子, 石澤有紀, 土屋浩一郎, 玉置俊晃, 冨田修平 : AngiotensinⅡ誘発血管リモデリングにおける血管平滑筋細胞内HIFシグナルの解析, 次世代を担う創薬・医療薬理シンポジウム2012, 2012年9月.
217.	田島壮一郎, 池田康将, 土屋浩一郎, 堀ノ内裕也, 櫻田巧, 木平孝高, 石澤有紀, 石澤啓介, 川添和義, 冨田修平, 水口和生, 玉置俊晃 : 十二指腸からの鉄吸収に対するAngiotensinⅡの影響, 第36回日本鉄バイオサイエンス学会学術集会, 2012年9月.
218.	前田悠作, 冨田修平, 村上正樹, 今西正樹, 木平孝高, 池田康将, 石澤啓介, 山野範子, 石澤有紀, 土屋浩一郎, 玉置俊晃 : 血管傷害モデルに伴う血管リモデリング形成過程には，傷害部位に動員される骨髄由来細胞のHIFが関与する, 第121回日本薬理学会近畿部会, 2012年6月.
219.	今西正樹, 冨田修平, 石澤啓介, 鈴木雄太, 木平孝高, 池田康将, 山野範子, 石澤有紀, 土屋浩一郎, 玉置俊晃 : 平滑筋特異的hypoxia-inducible factor-1α欠損がangiotensin II誘発血管リモデリング形成に及ぼす影響, 第121回日本薬理学会近畿部会, 2012年6月.
220.	池田康将, 田島壮一郎, 土屋浩一郎, 玉置俊晃 : 肥満進展における鉄と酸化ストレス, 第65回日本酸化ストレス学会学術集会シンポジウム「金属と酸化ストレスの関係を探る:基礎から臨床研究へ」, 2012年6月.
221.	石澤啓介, 櫻田巧, 今西正樹, 藤井聖子, 石澤有紀, 宮本理人, 山野範子, 木平孝高, 池田康将, 冨田修平, 土屋浩一郎, 玉置俊晃 : Nitrosonifedipine はangiotensin II 誘発のマウス血管リモデリングを改善する, 第65回日本酸化ストレス学会学術集会, 2012年6月.
222.	藤井聖子, 石澤啓介, 櫻田巧, 今西正樹, 石澤有紀, 木平孝高, 池田康将, 冨田修平, 土屋浩一郎, 玉置俊晃 : 糖尿病モデルマウスにおいてニトロソニフェジピンは腎症の進展を抑制する, 第55回日本腎臓学会学術総会, 2012年6月.
223.	中山泰介, 黒部裕嗣, 菅澤典子, 東田真由子, 吉田恭史, 佐田政隆, 玉置俊晃, 北川哲也, 冨田修平 : 小口径グラフト開存性改善を目的とするマクロファージHIF制御に関しての基礎研究, 第42回日本心臓血管外科学会学術総会, 2012年4月.
224.	三宅真理子, 木平孝高, 平田愛美, 石澤有紀, 石澤啓介, 池田康将, 土屋浩一郎, 玉置俊晃, 冨田修平 : 脂肪細胞における低酸素誘導因子1a欠損は高脂肪食負荷による耐糖能異常の発現を抑制する, 日本薬学会第132年会, 2012年3月.
225.	濱野修一, 香川葉子, 宮本理人, 石澤啓介, 土屋浩一郎, 玉置俊晃 : セスキテルペンラクトン誘導体の鉄依存ラジカル生成機構の検討, 日本薬学会大132年会, 2012年3月.
226.	布あさ美, 石澤啓介, 藤井聖子, 石澤有紀, 今西正樹, 櫻田巧, 木平孝高, 池田康将, 冨田修平, 土屋浩一郎, 玉置俊晃 : 2型糖尿病性腎症に対するニトロソニフェジピンの効果, 日本薬学会第132年会, 2012年3月.
227.	Yasumasa Ikeda, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Bovine Lactoferin Promotes Angiogenesis Via Akt-eNOS Dependent Pathway in Vascular Endothelial Cells, 第76回日本循環器学会学術集会, Mar. 2012.
228.	Taisuke Nakayama, Hirotsugu Kurobe, Noriko Sugasawa, Hajime Kinoshita, Mayuko Higashida, Yuuki Matsuoka, Mitsuru Takaku, Yasushi Yoshida, Yoichiro Hirata, Yousuke Takahama, Masataka Sata, Toshiaki Tamaki, Tetsuya Kitagawa and Shuhei Tomita : Role of Hypoxia-Inducible Factor1-alpha in Macrophage as an Aggravation Regulator in Development of Vascular Remodeling., 第76回日本循環器学会学術集会, Mar. 2012.
229.	榎本英明, 池田康将, 田島壮一郎, 石澤有紀, 木平孝高, 石澤啓介, 冨田修平, 土屋浩一郎, 玉置俊晃 : Protective effect of dietary iron restriction on diabetic nephropathy, 第85回日本薬理学会年会, 2012年3月.
230.	山野範子, 池田康将, 阪間稔, 石澤有紀, 木平孝高, 石澤啓介, 冨田修平, 土屋浩一郎, 玉置俊晃 : Accumulated iron storage in high fat diet-induced obese and diabetic mice, 第85回日本薬理学会年会, 2012年3月.
231.	藤井聖子, 石澤啓介, 櫻田巧, 石澤有紀, 今西正樹, 布あさ美, 鈴木雄太, 木平孝高, 池田康将, 冨田修平, 土屋浩一郎, 玉置俊晃 : Nitrosonifedipine prevents the progression of diabetic nephropathy in type 2 diabetic mice, 第85回日本薬理学会年会, 2012年3月.
232.	冨田修平, 高久暢, 山野範子, 石澤有紀, 木平孝高, 石澤啓介, 池田康将, 土屋浩一郎, 玉置俊晃 : Preoperative stabilization of HIF-1 by systemic introduction of dimethyloxalylglycine (DMOG), improves skin flap survival, 第85回日本薬理学会年会, 2012年3月.
233.	Masaki Imanishi, Keisuke Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Noriko Yamano, Yuki Izawa-Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki and Shuhei Tomita : The inhibitory effects of smooth muscle cell-specific hypoxia-inducible factor-1a deficiency on angiotensin 2-induced vascular remodeling in mice, 第85回日本薬理学会年会, Mar. 2012.
234.	Manami Hirata, Yoshitaka Kihira, Mariko Miyake, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya, Toshiaki Tamaki and Shuhei Tomita : High fat diet-induced inflammation in adipose tissues is reduced in adipocyte-specific hypoxia-inducible factor-1a knockout mice, 第85回日本薬理学会年会, Mar. 2012.
235.	石澤啓介, 藤井聖子, 布あさ美, 石澤有紀, 今西正樹, 櫻田巧, 木平孝高, 池田康将, 冨田修平, 土屋浩一郎, 玉置俊晃 : Nitrosonifedipineは2型糖尿病モデルマウスにおける腎症進展を抑制する, 第41回心脈管作動物質学会, 2012年2月.
236.	木平孝高, 三宅真理子, 平田愛美, 石澤有紀, 石澤啓介, 池田康将, 土屋浩一郎, 玉置俊晃, 冨田修平 : 肥満に伴う耐糖能異常の発現に対する脂肪細胞の低酸素誘導因子の役割, 第41回心脈管作動物質学会, 2012年2月.
237.	Noriko Yamano, Yasumasa Ikeda, Minoru Sakama, Soichiro Tajima, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : The alternation of iron metabolism in high fat diet-induced obese and diabetic mice, 第34回日本分子生物学会年会, Dec. 2011.
238.	池田康将, 榎本英明, 田島壮一郎, 石澤有紀, 木平孝高, 石澤啓介, 冨田修平, 土屋浩一郎, 玉置俊晃 : 糖尿病腎症進展における鉄除去の効果, 腎と高血圧update, 2011年12月.
239.	高久暢, 冨田修平, 木平孝高, 石澤有紀, 石澤啓介, 池田康将, 土屋浩一郎, 中西秀樹, 玉置俊晃 : PHD阻害剤の虚血皮弁生存拡大に対する効果, 第21回日本循環薬理学会, 2011年12月.
240.	谷口順平, 石澤啓介, 今西正樹, 木平孝高, 池田康将, 川添和義, 土屋浩一郎, 水口和生, 玉置俊晃, 冨田修平 : 血管平滑筋細胞のhypoxia-inducible factor-1αはangiotensinⅡ誘発血管リモデリングの形成に関与する, 第50回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2011年11月.
241.	櫻田巧, 石澤啓介, 今西正樹, 谷口順平, 藤井聖子, 布あさ美, 鈴木雄太, 宮本理人, 木平孝高, 土屋浩一郎, 川添和義, 水口和生, 玉置俊晃 : マウス血管リモデリングに対するnitrosonifedipineの抑制効果, 第50回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2011年11月.
242.	今西正樹, 石澤啓介, 木平孝高, 池田康将, 山野範子, 石澤有紀, 土屋浩一郎, 冨田修平, 玉置俊晃 : AngiotensinⅡ誘発性血管リモデリングは平滑筋特異的HIF-1α遺伝子欠損により抑制される, 第34回日本高血圧学会総会, 2011年10月.
243.	今西正樹, 石澤啓介, 木平孝高, 池田康将, 山野範子, 石澤有紀, 土屋浩一郎, 冨田修平, 玉置俊晃 : AngiotensinⅡ誘発性血管リモデリングは平滑筋特異的HIF-1α遺伝子欠損により抑制される, 第34回日本高血圧学会総会, 2011年10月.
244.	高久暢, 冨田修平, 木山明, 黒部裕嗣, 玉置俊晃, 橋本一郎, 中西秀樹 : 虚血皮弁生存に対するPHD阻害剤の効果, 第20回日本形成外科学会基礎学術集会, 2011年10月.
245.	田島壮一郎, 池田康将, 土屋浩一郎, 山野範子, 堀ノ内裕也, 櫻田巧, 木平孝高, 石澤有紀, 石澤啓介, 川添和義, 冨田修平, 水口和生, 玉置俊晃 : 肥満の脂肪組織における鉄の役割, 第35回日本鉄バイオサイエンス学会学術集会, 2011年9月.
246.	櫻田巧, 石澤啓介, 今西正樹, 谷口順平, 藤井聖子, 布あさ美, 鈴木雄太, 石澤有紀, 土屋浩一郎, 玉置俊晃 : Nitrosonifedipineによるマウス血管リモデリング抑制機構の解明, 次世代を担う創薬・医療薬理シンポジウム2011, 2011年8月.
247.	今西正樹, 石澤啓介, 木平孝高, 池田康将, 山野範子, 石澤有紀, 土屋浩一郎, 玉置俊晃, 冨田修平 : Hypoxia-inducible factor-1a in vascular smooth muscle cells contributes to the development of angiotensin -induced vascular remodeling, 第43回日本動脈硬化学会総会・学術集会, 2011年7月.
248.	赤池雅史, 土屋浩一郎, 柏田良樹, 高石喜久, 玉置俊晃, 岩瀬俊, 佐田政隆, 粟飯原賢一, 吉田守美子, 松本俊夫, 佐藤千穂, 西条伴香, 楊河宏章 : 生活習慣病関連リスクファクターに及ぼすスダチ果皮加工品の効果 ∼探索的臨床試験による検討∼, 第243回徳島医学会学術集会公開シンポジウム, 2011年7月.
249.	赤池雅史, 土屋浩一郎, 柏田良樹, 高石喜久, 玉置俊晃, 岩瀬俊, 佐田政隆, 粟飯原賢一, 吉田守実子, 松本俊夫, 佐藤千穂, 西条伴香, 楊河宏章 : 生活習慣病関連リスクファクターに及ぼすスダチ果皮加工品の効果-探索的臨床試験による検討-, 第243回徳島医学会学術集会, 2011年7月.
250.	谷口順平, 石澤啓介, 今西正樹, 木平孝高, 池田康将, 久次米敏秀, 川添和義, 土屋浩一郎, 水口和生, 玉置俊晃, 冨田修平 : 動脈硬化におけるhypoxia-inducible factor-1αの新規治療標的分子としての可能性, 医療薬学フォーラム2011/第19回クリニカルファーマシーシンポジウム, 2011年7月.
251.	今西正樹, 石澤啓介, 木平孝高, 池田康将, 山野範子, 石澤有紀, 土屋浩一郎, 玉置俊晃, 冨田修平 : AngiotensisⅡ誘発血管リモデリングは血管平滑筋細胞のhypoxia-inducible factor-1αを介して形成される, 第119回日本薬理学会近畿部会, 2011年7月.
252.	田島壮一郎, 池田康将, 土屋浩一郎, 堀ノ内裕也, 山野範子, 木平孝高, 石澤啓介, 川添和義, 冨田修平, 水口和生, 玉置俊晃 : ヒト腎糸球体血管内皮細胞において細胞内遊離鉄はangiotensin ⅡによるICAM-1の発現を増強する, 第54回日本腎臓学会学術集会, 2011年6月.
253.	高久暢, 冨田修平, 黒部裕嗣, 牛山明, 橋本一郎, 中西秀樹, 玉置俊晃 : 虚血皮弁生存に対するPHD阻害剤の効果, 第32回日本炎症・再生医学会, 2011年6月.
254.	池田康将, 田島壮一郎, 山野範子, 木平孝高, 石澤啓介, 冨田修平, 土屋浩一郎, 玉置俊晃 : 鉄除去薬による糖尿病の病態改善効果の検討, 第84回日本内分泌学会学術集会, 2011年4月.
255.	池田康将, 粟飯原賢一, 吉田守美子, 佐藤隆史, 赤池雅史, 玉置俊晃, 加藤茂明, 松本俊夫 : 心血管リモデリングにおける男性ホルモンの作用, 第84回日本内分泌学会学術集会シンポジウム「心血管病を内分泌・代謝面から考察する」, 2011年4月.
256.	Yasumasa Ikeda, Soichiro Tajima, Noriko Yamano, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Iron elimination ameliorated glucose tolerance through suppression of oxidative stress and inflammation on fat in diabetic mice, 第75回日本循環器学会総会・学術集会, Mar. 2011.
257.	Yasumasa Ikeda, Ken-ichi Aihara, Masashi Akaike, Sumiko Yoshida, Takashi Iwase, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Masataka Sata, Toshio Matsumoto and Toshiaki Tamaki : Heparin cofactor II enhances vascular endothelial cells function and angiogenesis, 第75回日本循環器学会総会・学術集会, Mar. 2011.
258.	Noriko Yamano, Yasumasa Ikeda, Minoru Sakama, Soichiro Tajima, Yoshitaka Kihira, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : The alternation of iron transport-related genes in high fat diet-induced obese and diabetic mice, 第84回日本薬理学会年会, Mar. 2011.
259.	Yoshitaka Kihira, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya, Shuhei Tomita and Toshiaki Tamaki : bFGF and insulin differentially regulate hypoxia-inducible factor-1 alpha in adipocytes, 第84回日本薬理学会年会, Mar. 2011.
260.	Yayoi Fukuhara, Shuhei Tomita, Masahisa Urata, Yoshitaka Kihira, Mitsuru Takaku, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : Role of HIF-1b in endothelial cells in monocrotaline-induced pulmonary hypertension, 第84回日本薬理学会年会, Mar. 2011.
261.	Yasumasa Ikeda, Soichiro Tajima, Sumiko Yoshida, Noriko Yamano, Yoshitaka Kihira, Keisuke Ishizawa, Ken-ichi Aihara, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Deferoxamine, an iron chelator, promotes revascularization via endothelial cells activation, 第84回日本薬理学会年会, Mar. 2011.
262.	Takumi Sakurada, Keisuke Ishizawa, Masaki Imanishi, Erika Tominaga, Junpei Taniguchi, Shoko Fujii, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Nitrosonifedipine, a photodegrative metabolite of nifedipine, improves angiotensin -induced vascular remodeling, 第84回日本薬理学会年会, Mar. 2011.
263.	Masaki Imanishi, Keisuke Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Koichiro Tsuchiya, Toshiaki Tamaki and Shuhei Tomita : Angiotensin -induced vascular remodeling is surpressed in smooth muscle cell-specific hypoxia-inducible factor-1a deficient mice, 第84回日本薬理学会年会, Mar. 2011.
264.	今西正樹, 石澤啓介, 櫻田巧, 富永えりか, 堀ノ内裕也, 谷口順平, 藤井聖子, 木平孝高, 池田康将, 冨田修平, 水口和生, 土屋浩一郎, 玉置俊晃 : Nitrosonifedipineによる血管リモデリング抑制効果の検討, 日本薬学会第131回年会, 2011年3月.
265.	堀ノ内裕也, 土屋浩一郎, 田島壮一郎, 木平孝高, 池田康将, 石澤啓介, 冨田修平, 川添和義, 玉置俊晃, 水口和生 : Nitrosonifedipine の細胞保護効果に関する検討, 日本薬学会第131年会, 2011年3月.
266.	高久暢, 冨田修平, 小谷武司, 橋本一郎, 中西秀樹, 玉置俊晃 : PHD阻害剤の虚血皮弁生存に対する効果, 第40回日本心脈管作動物質学会, 2011年2月.
267.	今西正樹, 石澤啓介, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃, 冨田修平 : AngiotensinⅡ誘発血管リモデリングにおけるhypoxia-inducible factor-1αの役割, 第40回日本心脈管作動物質学会, 2011年2月.
268.	田島壮一郎, 池田康将, 土屋浩一郎, 山野範子, 堀ノ内裕也, 木平孝高, 石澤啓介, 川添和義, 冨田修平, 水口和生, 玉置俊晃 : 鉄除去は脂肪肥大を抑制して糖尿病を改善する, 第40回日本心脈管作動物質学会, 2011年2月.
269.	櫻田巧, 石澤啓介, 今西正樹, 堀ノ内裕也, 富永えりか, 谷口順平, 藤井聖子, 木平孝高, 池田康将, 冨田修平, 土屋浩一郎, 玉置俊晃 : AngiotensinⅡ誘発血管リモデリングに対するニトロソニフェジピンの抑制作用, 第40回日本心脈管作動物質学会, 2011年2月.
270.	池田康将, 田島壮一郎, 吉田守美子, 山野範子, 木平孝高, 石澤啓介, 粟飯原賢一, 冨田修平, 土屋浩一郎, 玉置俊晃 : マウス下肢虚血モデルにおいて鉄キレート剤Deferoxamineは酸化ストレスとアポトーシスを抑制する, 第40回日本心脈管作動物質学会, 2011年2月.
271.	山野範子, 池田康将, 田島壮一郎, 木平孝高, 石澤啓介, 冨田修平, 土屋浩一郎, 玉置俊晃 : 高脂肪食負荷肥満マウスにおける鉄吸収動態の検討, 第40回日本心脈管作動物質学会, 2011年2月.
272.	田島壮一郎, 池田康将, 土屋浩一郎, 山野範子, 堀ノ内裕也, 木平孝高, 石澤啓介, 川添和義, 冨田修平, 水口和生, 玉置俊晃 : 鉄除去は脂肪肥大を抑制して糖尿病を改善する, 第40回日本心脈管作動物質学会, 2011年2月.
273.	櫻田巧, 石澤啓介, 今西正樹, 堀ノ内裕也, 富永えりか, 谷口順平, 藤井聖子, 木平孝高, 池田康将, 冨田修平, 土屋浩一郎, 玉置俊晃 : AngiotensinⅡ誘発血管リモデリングに対するニトロソニフェジピンの抑制作用, 第40回日本心脈管作動物質学会, 2011年2月.
274.	今西正樹, 石澤啓介, 木平孝高, 池田康将, 土屋浩一郎, 玉置俊晃, 冨田修平 : AngiotensinⅡ誘発血管リモデリングにおけるhypoxia-inducible factor-1αの役割, 第40回日本心脈管作動物質学会, 2011年2月.
275.	黒部裕嗣, 冨田修平, 神原保, 北川哲也, 玉置俊晃 : 血管リモデリングに対してT細胞のHIF-1aは抑制的に機能する, 第18回日本血管生物学学会, 2010年12月.
276.	池田康将, 田島壮一郎, 吉田守美子, 山野範子, 木平孝高, 石澤啓介, 粟飯原賢一, 冨田修平, 土屋浩一郎, 玉置俊晃 : Deferoxamine, an iron chelator, enhances angiogenesis through Akt-eNOS-dependent pathway in endothelial cells, 第18回日本血管生物医学会学術集会, 2010年12月.
277.	Yuuko Imamura, Yoshitaka Kihira, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya, Shuhei Tomita and Toshiaki Tamaki : HIF-2/ARNT control hair differentiation by up-regulating p21Waf1/Cip1, 第33回日本分子生物学会年会, Dec. 2010.
278.	木平孝高, 石澤啓介, 池田康将, 土屋浩一郎, 冨田修平, 玉置俊晃 : 脂肪細胞における塩基性繊維芽細胞増殖因子による低酸素誘導因子誘導とそれを介した糖輸送担体発現誘導, 第118回日本薬理学会近畿部会, 2010年11月. (キーワード) 第118回日本薬理学会近畿部会
279.	富永えりか, 石澤啓介, 今西正樹, 櫻田巧, 谷口順平, 藤井聖子, 堀ノ内裕也, 木平孝高, 阿部真治, 川添和義, 土屋浩一郎, 玉置俊晃, 水口和生 : アンジオテンシンII による血管リモデリングに対するニトロソニフェジピンの影響, 第49回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2010年11月.
280.	田島壮一郎, 池田康将, 堀ノ内裕也, 木平孝高, 冨田修平, 山野範子, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 鉄キレート剤 deferoxamine は内皮細胞活性化により血管新生を促進する, 第20回日本循環薬理学会, 2010年11月.
281.	土屋浩一郎, 石澤啓介, 木平孝高, 池田康将, 冨田修平, 玉置俊晃 : 亜硝酸塩由来血中NO動態に与える経口鉄の影響, 第22回腎とフリーラジカル研究会, 2010年10月.
282.	今西正樹, 石澤啓介, 富永えりか, 櫻田巧, 堀ノ内裕也, 谷口順平, 藤井聖子, 木平孝高, 池田康将, 冨田修平, 土屋浩一郎, 玉置俊晃 : Angiotensin II による血管平滑筋細胞の遊走および増殖に対するnifedipine代謝物の抑制作用とそのメカニズム, 第33回日本高血圧学会, 2010年10月.
283.	田島壮一郎, 池田康将, 土屋浩一郎, 山野範子, 堀ノ内裕也, 木平孝高, 石澤啓介, 川添和義, 冨田修平, 水口和生, 玉置俊晃 : 2型糖尿病モデルマウスに対する鉄キレート剤による糖尿病改善効果の検討, 第34回日本鉄バイオサイエンス学会学術集会, 2010年9月.
284.	藤井聖子, 石澤啓介, 今西正樹, 富永えりか, 桜田巧, 谷口順平, 堀ノ内裕也, 木平孝高, 池田康将, 冨田修平, 玉置俊晃, 土屋浩一郎 : AngiotensinⅡ誘発血管リモデリングに対するnitrosonifedipineの抑制効果, 次世代を担う創薬・医療薬理シンポジウム2010, 2010年9月.
285.	冨田修平, 木平孝高, 池田康将, 石澤啓介, 土屋浩一郎, 玉置俊晃 : 動脈硬化に伴う血管リモデリングに対してT細胞のHIF-1 は抑制的に機能する．, 第31回日本炎症再生医学会, 2010年8月.
286.	今西正樹, 石澤啓介, 富永えりか, 堀ノ内裕也, 谷口順平, 藤井聖子, 木平孝高, 池田康将, 冨田修平, 土屋浩一郎, 玉置俊晃 : Nifedipine代謝物によるangiotensin II 誘発血管平滑筋細胞遊走及び増殖に対する抑制作用, 第117回日本薬理学会近畿部会, 2010年7月.
287.	石澤啓介, 今西正樹, Erika Tminaga, 堀ノ内裕也, Takumi Sakurada, Zyunpei Taniguchi, Seiko Fujii, 木平孝高, 池田康将, 冨田修平, 玉置俊晃, 土屋浩一郎 : Nifedipine代謝物はangiotensinⅡによる血管平滑筋細胞遊走および増殖を抑制する, 第63回日本酸化ストレス学会, 2010年6月.
288.	池田康将, 土屋浩一郎, 田島壮一郎, 堀ノ内裕也, 木平孝高, 石澤啓介, 冨田修平, 高石喜久, 玉置俊晃 : 徳島県名産スダチ果皮の抗生活習慣病作用, 第83回日本薬理学会年会シンポジウム「肥満の栄養ゲノミクスと薬理ゲノミクス」, 2010年3月.
289.	冨田修平, 木平孝高, 福原弥生, 桜田巧, 今西正樹, 玉置俊晃 : 病態に観られる低酸素応答の意義-血管リモデリングにおけるT細胞のHIF-1の役割-, 第83回日本薬理学会年会シンポジウム「病態における低酸素応答機構の解明と治療への応用」, 2010年3月.
290.	石澤啓介, 吉栖正典, Dortsuren Naruantungalag, 今村優子, 池田康将, 寺尾純二, 土屋浩一郎, 玉置俊晃 : ケルセチンの生体内代謝と動脈硬化予防効果, 第83回日本薬理学会年会シンポジウム「健康食品の薬理学」, 2010年3月.
291.	冨田修平, 木平孝高, 福原弥生, 桜田巧, 今西正樹, 玉置俊晃 : 病態に観られる低酸素応答の意義-血管リモデリングにおけるT細胞のHIF-1の役割-, 第83回日本薬理学会年会シンポジウム「病態における低酸素応答機構の解明と治療への応用」, 2010年3月.
292.	田島壮一郎, 池田康将, 土屋浩一郎, 堀ノ内裕也, 櫻田巧, 木平孝高, 石澤啓介, 川添和義, 冨田修平, 水口和生, 玉置俊晃 : KK-Ay マウスにおける鉄キレート剤Deferoxamineによる糖尿病病態改善効果の検討, 第83回日本薬理学会, 2010年3月.
293.	黒部裕嗣, 浦田将久, 福原弥生, 神原保, 粟飯原賢一, 赤池雅史, 高浜洋介, 玉置俊晃, 松本俊夫, 冨田修平, 北川哲也 : 血管リモデリング時の転写因子HIF-1αの役割 (第110回日本外科学会定期学術集会), 日本外科学会雑誌, Vol.111, No.2, 701, 2010年3月. (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1572543027394884480 (CiNii: 1572543027394884480)
294.	福原弥生, 冨田修平, 木平孝高, 池田康将, 石澤啓介, 土屋浩一郎, 吉栖正典, 玉置俊晃 : T細胞のHIF-1aは，動脈硬化に伴う血管リモデリングを抑制的に制御する, 第39回日本心脈管作動物質学会, 2010年2月.
295.	池田康将, 木平孝高, 石澤啓介, 冨田修平, 玉置俊晃 : 鉄キレート剤 Deferoxamine の血管新生左葉―マウス下肢虚血モデルにおける検討―, 第39回日本心脈管作動物質学会, 2010年2月.
296.	富永えりか, 石澤啓介, 櫻田巧, 今西正樹, 谷口順平, 川添和義, 木平孝高, 池田康将, 冨田修平, 土屋浩一郎, 水口和生, 玉置俊晃 : Angiotensin IIによる血管平滑筋細胞遊走に対するnifedipine代謝物の影響, 第30回日本臨床薬理学会年会, 2009年12月.
297.	富永えりか, 石澤啓介, 櫻田巧, 今西正樹, 谷口順平, 山﨑有希子, 木平孝高, 川添和義, 土屋浩一郎, 水口和生, 玉置俊晃 : ニフェジピン代謝物はアンジオテンシンⅡ誘発血管平滑筋細胞遊走を抑制する, 第48回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2009年11月.
298.	山﨑有希子, 石澤啓介, 富永えりか, 谷口順平, 櫻田巧, 川添和義, 土屋浩一郎, 玉置俊晃, 水口和生 : アンジオテンシンⅡによる血管平滑筋細胞遊走・増殖における細胞内鉄の関与, 第48回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2009年11月.
299.	福原弥生, 冨田修平, 浦田将久, 木平孝高, 池田康将, 石澤啓介, 土屋浩一郎, 玉置俊晃 : モノクロタリン誘導肺高血圧症モデルマウスにおける血管内皮細胞の低酸素応答因子(HIF-1b)の役割, 第116回日本薬理学会近畿部会, 2009年6月.
300.	木平孝高, 御園生裕明, 石澤啓介, 池田康将, 冨田修平, 玉置俊晃 : 電位依存性Kチャネル Kv2.1とKv2.2の相互作用, 第115回日本薬理学会近畿部会, 2009年6月.
301.	田島壮一郎, 土屋浩一郎, 濱本磨以, 堀ノ内裕也, 冨田修平, 石澤啓介, 川添和義, 玉置俊晃, 水口和生 : Angiotensin IIによるヒト腎糸球体血管内皮細胞(HGEC)内における鉄動態の検討, 日本薬学会129年会, 2009年3月.
302.	廣永有沙, 石澤啓介, 山崎有希子, 野瀬文乃, 川添和義, 玉置俊晃, 水口和生 : オルメサルタンはPDGF誘導メサンギウム細胞遊走をAT1受容体非依存的に抑制する, 第47回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 189, 2008年11月.
303.	渡邊政博, 山本武範, 角幡玲, 岡田直人, 梶本和昭, 山﨑尚志, 片岡正俊, 馬場嘉信, 玉置俊晃, 篠原康雄 : 褐色脂肪組織の機能亢進に関与する新規因子の探索, 第6回ファーマ・バイオフォーラム 2007, 2007年12月.
304.	田岡千明, 土屋浩一郎, 神谷昌樹, 根本尚夫, 石澤啓介, 山口邦久, 滝口祥令, 玉置俊晃 : 水溶性Fenofibrate製剤の作成と中性脂肪低下作用の検討, 第111回日本薬理学会近畿部会, 81, 2007年6月.
305.	松村敏彦, 宮本由加里, 黒川ふみ, 阿部真治, 榊原啓之, 石澤啓介, 土屋浩一郎, 清水寛, 寺尾純二, 玉置俊晃, 川添和義, 水口和生 : ラット強制水泳試験における漢方薬の抗うつ作用の検討, 第45回日本薬学会・日本病院薬剤師会中国四国支部学術大会, 125, 2006年10月.
306.	平広範, 石澤啓介, 廣永有沙, 川添和義, 玉置俊晃, 水口和生 : 血管内皮細胞障害におけるアンジオテンシンII受容体拮抗薬の保護効果, 第45回日本薬学会・日本病院薬剤師会中国四国支部学術大会, 102, 2006年10月.
307.	川添和義, 松村敏彦, 黒川ふみ, 榊原啓之, 石澤啓介, 土屋浩一郎, 清水寛, 寺尾純二, 玉置俊晃, 水口和生 : ラット強制水泳試験による漢方薬の抗うつ作用評価, 第109回日本薬理学会近畿部会, 30, 2006年6月.
308.	Hirotsugu Kurobe, Yuki Izawa, Yayoi Fukumura, Tamotsu Kanbara, Atsushi Kurushima, Ken-ichi Aihara, Masashi Akaike, Masashi Kano, Takashi Kitaichi, Yutaka Masuda, Hiroyuki Azuma, Toshiaki Tamaki, Toshio Matsumoto, Tetsuya Kitagawa, Shuhei Tomita and Masanori Yoshizumi : HIF-ARNT transcriptional system in T cells has a pivotal role in vascular in flammation and remodeling., 第70回日本循環器学会学術総会, Mar. 2006.
309.	黒部裕嗣, 冨田修平, 井澤有紀, 福原弥生, 神原保, 粟飯原賢一, 赤池雅史, 北川哲也, 松本俊夫, 吉栖正典, 玉置俊晃 : T細胞特異的HIF1αKOマイスではカフモデルにて血管リモデリングが促進される, 第15回日本循環薬理学会, 2005年11月.
310.	森口博基, 片山貴文, 玉置俊晃, 寺嶋吉保, 山本誠 : 「Tutorial Hybrid System」の開発と運用, 医療情報学22回連合大会論文集, 476-477, 2002年11月.

その他・研究会:

1.	池田裕美子, 斎藤尚子, 石澤有紀, 堀ノ内裕也, 池田康将, 石澤啓介, 玉置俊晃 : ケルセチンによる血管保護効果の検討, 西日本医学生学術フォーラム(第5回医学研究学生フォーラム), 2016年12月.
2.	座間味義人, 今西正樹, 武智研志, 堀ノ内裕也, 宮本理人, 石澤有紀, 池田康将, 玉置俊晃, 石澤啓介 : ドラッグリポジショニング手法を用いた新規循環器治療薬の探索研究, 第23回大阪市大フォーラム, 2016年8月.
3.	津田勝範, 宮本理人, 森本悠里, 濱野修一, 石澤啓介, 木平考高, 池田康将, 玉置俊晃, 土屋浩一郎 : 鉄過剰ストレスに対するニトロソニフェジピン(NO-NIF)の抗酸化メカニズム検討, 徳島医学会, 2015年8月.

報告書:

1.	桐山聰, 英崇夫, 荒木秀夫, 中村浩一, 黒岩眞吾, 藤澤正一郎, 原口雅宣, 玉置俊晃, 羽地達次, 高石喜久, 來山征士, 大橋眞, 上田哲史 : 特色ある大学教育支援プログラム「進取の気風」を育む創造性教育の推進平成17年度報告書, --- 若者のセルフ·マネジメント能力を育てる徳島大学創成学習開発センターの活動 ---, 特色ある大学教育支援プログラム「進取の気風」を育む創造性教育の推進平成17年度報告書, 徳島, 2006年3月.
2.	吉栖正典, 石澤啓介, 土屋浩一郎, 玉置俊晃 : インスリン抵抗性に対するロサルタンおよびロサルタンと運動の併用による効果-モデルラットを用いたin vivoでの検討-, 第17回健康医科学研究助成論文集, No.17, 124-134, 東京, 2002年3月.

特許:

1.	玉置俊晃, 池田康将, 土屋浩一郎 : マクロファージの浸潤抑制によるインスリン抵抗性改善剤, (2011年), 特許第2011-174001号 (2011年).

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

慢性腎臓病の発症・進展におけるADAM17の役割解明 (研究課題/領域番号: 17K10144 )
食事性亜硝酸によるエピゲノム修飾に対する作用と生理的役割解明 (研究課題/領域番号: 15H02898 )
食餌性由来亜硝酸塩によるAMPK活性化機構の解明 (研究課題/領域番号: 25460332 )
血管構築細胞の低酸素誘導性形質転換の分子機序の解明 (研究課題/領域番号: 24590381 )
糖尿病性腎症モデルラットにおける亜硝酸塩による腎保護作用の検討 (研究課題/領域番号: 22590241 )
血管内皮細胞の低酸素誘導性形質変化の分子機序の解明 (研究課題/領域番号: 21590335 )
血管内皮細胞における低酸素シグナルによる炎症誘発性応答機構の解明 (研究課題/領域番号: 19590281 )
生体内における亜硝酸由来NO生成因子の解明 (研究課題/領域番号: 18590235 )
高等教育改革のコミュニケーション分析-現場における文化変容の質的検討- (研究課題/領域番号: 18330105 )
亜硝酸由来の新しい一酸化窒素産生系の生理的・病態生理的役割の解明 (研究課題/領域番号: 17390066 )
腎虚血-再潅流時の腎臓内亜硝酸由来NO産生の病態生理学的役割の解明 (研究課題/領域番号: 16590196 )
糖尿病性微小血管障害での新規MAPキナーゼ、BMK1の生理的役割の解明と分子創薬 (研究課題/領域番号: 16590195 )
医学教育のエスノメソドロジー-医療面接実習とOSCEの相互行為的基礎 (研究課題/領域番号: 15330100 )
糖尿病性腎症での新規MAPキナーゼ、BMK1の役割解明とそれを標的とした分子創薬 (研究課題/領域番号: 14570078 )
腎臓の虚血再灌流障害における活性窒素種の産生機序と障害に対する役割解明 (研究課題/領域番号: 13670087 )
エンドセリン(1-31)の炎症性疾患に対する病態生理学的役割解明 (研究課題/領域番号: 12557008 )
損傷脊髄における脊髄循環障害の病態ならびに本能的治療法開発に関する研究 (研究課題/領域番号: 11470311 )
新規血管作道性ペプチド、エンドセリン(1-31)の腎障害に及ぼす役割の解明 (研究課題/領域番号: 10670085 )
尿細管糸球体フィードバック機構の解明-糸球体輸入細動脈と尿細管の個別潅流法を用いて- (研究課題/領域番号: 06454161 )
実質臓器透析用ファイバー型プローブの開発 (研究課題/領域番号: 04557010 )
細動脈レベルにおける腎循環調節機序-糸球体輸入・輸出細動脈における酵素活性の相違- (研究課題/領域番号: 03454145 )
細動脈レベルにおける腎循環調節機序-輪入、輪出細動脈における酵素活性の相違- (研究課題/領域番号: 62570089 )
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名誉教授 : 玉置 俊晃

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科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

名誉教授 : 玉置俊晃