Tokushima University / Educator and Researcher Directory --- Nikawa, Takeshi

Personal Web Page

https://researchmap.jp/read0184061 (researchmap)

Field of Study

○	Health Studies

Subject of Study

○

Book / Paper

Book:

1.	Katsuyuki Miyawaki, Mutsumi Aihara, Akira Takahashi and Takeshi Nikawa : LEDを用いた近未来宇宙植物工場の開発, Technical Information Institute Co., Ltd., Apr. 2020.
2.	Takayuki Uchida and Takeshi Nikawa : 微小重力環境における筋萎縮発生メカニズムへの新展開, HOKURYUKAN, Tokyo, Oct. 2018. (Keyword) mitochondria / muscle atrophy
3.	Masashi Masuda, 新井田裕樹, Yutaka Taketani and Takeshi Nikawa : ビタミンD欠乏とサルコペニアについて, Kodansha, Tokyo, Apr. 2018.
4.	Takayuki Uchida and Takeshi Nikawa : サルコペニア発症におけるメカニカルストレスの関与, Apr. 2016. (Keyword) muscle / oxidative stress
5.	Tomoki Abe, 河野尚平, Katsuya Hirasaka and Takeshi Nikawa : 骨格筋症候群(第2版)下ーその他の神経筋疾患を含めてー, --- Space flight and muscle atrophy ---, NIPPONRINSHOSHA Co.,Ltd., Tokyo, Jul. 2015. (Keyword) IGF-1 / 宇宙フライト / 骨格筋萎縮 / タンパク質分解 / ユビキチン-プロテアソーム系
6.	林淳三, 木本幸一, 鈴木和春, 塚原典子, Takeshi Nikawa, Shigetada Kondo, 松田早苗, 山本孝史, 薗田勝 and Tomoki Abe : Nブックス三訂基礎栄養学, KENPAKUSHA, Tokyo, Feb. 2015.
7.	Junji Terao, Rie Mukai, Yamashita Y., Ochi Arisa, Kohno Shohei, Katsuya Hirasaka and Takeshi Nikawa : Chapter 7. Food Functions Preventing Muscle Atrophy., 2014.
8.	Rie Mukai, Takeshi Nikawa and Junji Terao : フラボノイドによる廃用性筋萎縮予防, 株式会社シーエムシー出版, Oct. 2013.
9.	Rie Mukai, Hisao Nemoto, Takeshi Nikawa and Junji Terao : Physiological functions of prenylated flavonoids, The Vitamin Society of Japan, Feb. 2013. (Keyword) Prenylated flavonoids / Disuse muscle atrophy / Sarcopenia / Ubiquitin ligase / Isoprenoid (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390001205669531264 (CiNii: 1390001205669531264)
10.	Takeshi Nikawa : 管理栄養士講座「人体の構造と機能」, KENPAKUSHA, Tokyo, Dec. 2005.
11.	Takeshi Nikawa : 管理栄養士養成シリーズ5 解剖生理学高野康夫編, Kagaku-Dojin Publishing Company,INC, Kyoto, Oct. 2004.
12.	Takeshi Nikawa, 浅野間友紀 and Kyoichi Kishi : 栄養と生体応答?遺伝子と免疫の視点から, 昭和堂, 京都, Apr. 2004.
13.	Takeshi Nikawa : 最新「運動生理化学実験法」分子・細胞・組織レベルからのアプローチ, 大修館書店, Tokyo, Jul. 1998. (Summary) 運動生理学の研究者を対象に，その分子・細胞・組織レベルの実験方法を分かりやすく解説した．
14.	Kyoichi Kishi, Arinobu Yamauchi, Fujiko Shizuka, Yasuhiro Kido, Takeshi Nikawa and Kazuhito Rokutan : Serotonin in the Central Nervous System and Periphery, --- Effect of macronutrient intakes on brain serotonin metabolite as measured by in vivo microdialysis in the rat ---, Elsevier, Tokyo, Apr. 1995.
15.	Nobuhiko Katunuma, Hisao Kakegawa, Y Matsunaga, Takeshi Nikawa and Eiki Kominami : Agents Actions:Proreases,Protease Inhibitors and Protease-Drived Peptides(JC Cheronis and JE repine,eds), --- Different functional share of individual lysosomal cathepsins in normal and pathological conditions ---, Birkhauser Verlag, May 1993.

Academic Paper (Judged Full Paper):

1.	Takayuki Uchida, Kohno Madoka, Chinami Itoh, Erika Yamano, Hiroki Matsuki, MIZANUR MD Rahman, ANAYT ULLA, Minori Suzuki, Takahiro Ishiguro and Takeshi Nikawa : Inhibitory Effect of Kori-tofu Protein on Denervation-Induced Atrogene Expression in Mouse Skeletal Muscle, Biological Sciences in Space, Vol.38, 1-7, 2024.
2.	Yurika Ito, Mari Yamagata, Takuya Yamamoto, Katsuya Hirasaka, Takeshi Nikawa and Takahiko Sato : The reciprocal regulation between mitochondrial-associated membranes and Notch signaling in skeletal muscle atrophy., eLife, Vol.12, RP89381, 2023. (Summary) Skeletal muscle atrophy and the inhibition of muscle regeneration are known to occur as a natural consequence of aging, yet the underlying mechanisms that lead to these processes in atrophic myofibers remain largely unclear. Our research has revealed that the maintenance of proper mitochondrial-associated endoplasmic reticulum membranes (MAM) is vital for preventing skeletal muscle atrophy in microgravity environments. We discovered that the deletion of the mitochondrial fusion protein Mitofusin2 (MFN2), which serves as a tether for MAM, in human induced pluripotent stem (iPS) cells or the reduction of MAM in differentiated myotubes caused by microgravity interfered with myogenic differentiation process and an increased susceptibility to muscle atrophy, as well as the activation of the Notch signaling pathway. The atrophic phenotype of differentiated myotubes in microgravity and the regenerative capacity of Mfn2-deficient muscle stem cells in dystrophic mice were both ameliorated by treatment with the gamma-secretase inhibitor DAPT. Our findings demonstrate how the orchestration of mitochondrial morphology in differentiated myotubes and regenerating muscle stem cells plays a crucial role in regulating Notch signaling through the interaction of MAM. (Keyword) Mice / Humans / Animals / Muscular Atrophy / Muscle Fibers, Skeletal / Signal Transduction / Mitochondria / Weightlessness / Muscle, Skeletal (Link to Publication Site) ● Publication site (DOI): 10.7554/eLife.89381 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38099641 ● Search Scopus @ Elsevier (PMID): 38099641 ● Search Scopus @ Elsevier (DOI): 10.7554/eLife.89381 (DOI: 10.7554/eLife.89381, PubMed: 38099641)
3.	Shintaro Inoue, Takahito Watanabe, Taiki Hamaguchi, Yoshiyasu Ishimaru, Katsuyuki Miyawaki, Takeshi Nikawa, Akira Takahashi, Sumihare Noji and Taro Mito : Combinatorial expression of ebony and tan generates body color variation from nymph through adult stages in the cricket, Gryllus bimaculatus., PLoS ONE, Vol.18, No.5, 2023. (Summary) Insect body colors and patterns change markedly during development in some species as they adapt to their surroundings. The contribution of melanin and sclerotin pigments, both of which are synthesized from dopamine, to cuticle tanning has been well studied. Nevertheless, little is known about how insects alter their body color patterns. To investigate this mechanism, the cricket Gryllus bimaculatus, whose body color patterns change during postembryonic development, was used as a model in this study. We focused on the ebony and tan genes, which encode enzymes that catalyze the synthesis and degradation, respectively, of the precursor of yellow sclerotin N-β-alanyl dopamine (NBAD). Expression of the G. bimaculatus (Gb) ebony and tan transcripts tended to be elevated just after hatching and the molting period. We found that dynamic alterations in the combined expression levels of Gb'ebony and Gb'tan correlated with the body color transition from the nymphal stages to the adult. The body color of Gb'ebony knockout mutants generated by CRISPR/Cas9 systemically darkened. Meanwhile, Gb'tan knockout mutants displayed a yellow color in certain areas and stages. The phenotypes of the Gb'ebony and Gb'tan mutants probably result from an over-production of melanin and yellow sclerotin NBAD, respectively. Overall, stage-specific body color patterns in the postembryonic stages of the cricket are governed by the combinatorial expression of Gb'ebony and Gb'tan. Our findings provide insights into the mechanism by which insects evolve adaptive body coloration at each developmental stage. (Keyword) Animals / Melanins / Gryllidae / Nymph / Dopamine / Insect Proteins (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0285934 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37200362 ● Search Scopus @ Elsevier (PMID): 37200362 ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0285934 (DOI: 10.1371/journal.pone.0285934, PubMed: 37200362)
4.	Taishi Kondo, Tomoaki Ishida, Ke Ye, Marin Muraguchi, Yohei Tanimura, Masato Yoshida, Kan'ichiro Ishiuchi, Tomoki Abe, Takeshi Nikawa, Keisuke Hagihara, Hidetoshi Hayashi and Toshiaki Makino : Correction to: Suppressive effects of processed aconite root on dexamethasone-induced muscle ring finger protein-1 expression and its active ingredients., Journal of Natural Medicines, Vol.76, No.3, 594-604, 2023. (Link to Publication Site) ● Publication site (DOI): 10.1007/s11418-023-01691-0 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36929460 ● Search Scopus @ Elsevier (PMID): 36929460 ● Search Scopus @ Elsevier (DOI): 10.1007/s11418-023-01691-0 (DOI: 10.1007/s11418-023-01691-0, PubMed: 36929460)
5.	Luchuanyang Sun, Sangeun Kim, Ryoichi Mori, Nobuyuki Miyaji, Takeshi Nikawa and Katsuya Hirasaka : Astaxanthin Exerts Immunomodulatory Effect by Regulating SDH-HIF-1α Axis and Reprogramming Mitochondrial Metabolism in LPS-Stimulated RAW264.7 Cells., Marine Drugs, Vol.20, No.11, 660, 2022. (Summary) production and maintained the mitochondrial membrane potential, implying that AX preserved mitochondrial homeostasis to avoid LPS stimulation-induced mitochondrial dysfunction. Additionally, AX prevented the decrease in mitochondrial complexes I, II, and III, which were caused by LPS stimulation. Especially, AX inhibited the reduction in mitochondrial succinate dehydrogenase (SDH; complex II) activity and upregulated the protein and mRNA level of SDH complex, subunit B. Furthermore, AX blocked the IL-1β expression by regulating the SDH-HIF-1α axis and suppressed the energy shift from an OXPHOS phenotype to a glycolysis phenotype. These findings revealed important effects of AX on mitochondrial enzymes as well as on mitochondrial energy metabolism in the immune response. In addition, these raised the possibility that AX plays an important role in other diseases caused by SDH mutation and metabolic disorders. (Keyword) Lipopolysaccharides / Succinate Dehydrogenase / Mitochondria / Immunity / Hypoxia-Inducible Factor 1, alpha Subunit (Tokushima University Institutional Repository) ● Metadata: 118918 (Link to Publication Site) ● Publication site (DOI): 10.3390/md20110660 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36354983 ● Search Scopus @ Elsevier (PMID): 36354983 ● Search Scopus @ Elsevier (DOI): 10.3390/md20110660 (Tokushima University Institutional Repository: 118918, DOI: 10.3390/md20110660, PubMed: 36354983)
6.	ANAYT ULLA, Kanae Osaki, Mizanur Md Rahman, Reiko Nakao, Takayuki Uchida, Isafumi Maru, Kazuaki Mawatari, Tomoya Fukawa, Hiro-omi Kanayama, Iori Sakakibara, Katsuya Hirasaka and Takeshi Nikawa : Morin improves dexamethasone-induced muscle atrophy by modulating atrophy-related genes and oxidative stress in female mice., Bioscience, Biotechnology, and Biochemistry, Vol.86, No.10, 1448-1458, 2022. (Summary) This study investigated the effect of morin, a flavonoid, on dexamethasone-induced muscle atrophy in C57BL/6J female mice. Dexamethasone (10 mg/kg body weight) for 10 days significantly reduced body weight, gastrocnemius and tibialis anterior muscle mass, and muscle protein in mice. Dexamethasone significantly upregulated muscle atrophy-associated ubiquitin ligases, including atrogin-1 and MuRF-1, and the upstream transcription factors FoxO3a and Klf15. Additionally, dexamethasone significantly induced the expression of oxidative stress-sensitive ubiquitin ligase Cbl-b and the accumulation of the oxidative stress markers malondialdehyde and advanced protein oxidation products in both the plasma and skeletal muscle samples. Intriguingly, morin treatment (20 mg/kg body weight) for 17 days effectively attenuated the loss of muscle mass and muscle protein and suppressed the expression of ubiquitin ligases while reducing the expression of upstream transcriptional factors. Therefore, morin might act as a potential therapeutic agent to attenuate muscle atrophy by modulating atrophy-inducing genes and preventing oxidative stress. (Keyword) Animals / Body Weight / Dexamethasone / Female / Flavones / Malondialdehyde / Mice / Mice, Inbred C57BL / Muscle Proteins / Muscle, Skeletal / Muscular Atrophy / Oxidative Stress / Tripartite Motif Proteins / Ubiquitin-Protein Ligases (Link to Publication Site) ● Publication site (DOI): 10.1093/bbb/zbac140 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35977398 ● Search Scopus @ Elsevier (PMID): 35977398 ● Search Scopus @ Elsevier (DOI): 10.1093/bbb/zbac140 (DOI: 10.1093/bbb/zbac140, PubMed: 35977398)
7.	Min Yang, Luchuanyang Sun, Yasunosuke Kawabata, Fumihito Murayama, Takahiro Maegawa, Takeshi Nikawa and Katsuya Hirasaka : Balenine, Imidazole Dipeptide Promotes Skeletal Muscle Regeneration by Regulating Phagocytosis Properties of Immune Cells., Marine Drugs, Vol.20, No.5, 313, 2022. (Summary) Balenine is one of the endogenous imidazole dipeptides derived from marine products. It is composed of beta-alanine and 3-methyl-L-histidine, which exist mainly in the muscles of marine organisms. The physiological functions of dietary balenine are not well-known. In this study, we investigated whether the supplementation of dietary balenine was associated with muscle function in a cardiotoxin-indued muscle degeneration/regeneration model. Through morphological observation, we found that the supplementation of balenine-enriched extract promoted the regeneration stage. In addition, the expression of regeneration-related myogenic marker genes, such as paired box protein 7, MyoD1, myogenin, and Myh3, in a group of mice fed a balenine-enriched extract diet was higher than that in a group fed a normal diet. Moreover, the supplementation of balenine-enriched extract promoted the expression of anti-inflammatory cytokines as well as pro-inflammatory cytokines at the degeneration stage. Interestingly, phagocytic activity in the balenine group was significantly higher than that in the control group in vitro. These results suggest that balenine may promote the progress of muscle regeneration by increasing the phagocytic activity of macrophages. (Keyword) Animals / Cytokines / Dipeptides / Imidazoles / Macrophages / Mice / Muscle, Skeletal / Phagocytosis (Tokushima University Institutional Repository) ● Metadata: 118917 (Link to Publication Site) ● Publication site (DOI): 10.3390/md20050313 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35621964 ● Search Scopus @ Elsevier (PMID): 35621964 ● Search Scopus @ Elsevier (DOI): 10.3390/md20050313 (Tokushima University Institutional Repository: 118917, DOI: 10.3390/md20050313, PubMed: 35621964)
8.	Yuichiro Adachi, Masashi Masuda, Iori Sakakibara, Takayuki Uchida, Yuki Niida, Yuki Mori, Yuki Kamei, Yosuke Okumura, Hirokazu Ohminami, Kohta Ohnishi, Hisami Okumura, Takeshi Nikawa and Yutaka Taketani : All-trans retinoic acid changes muscle fiber type via increasing GADD34 dependent on MAPK signal., Life Science Alliance, Vol.5, No.7, 2022. (Summary) All-trans retinoic acid (ATRA) increases the sensitivity to unfolded protein response in differentiating leukemic blasts. The downstream transcriptional factor of PERK, a major arm of unfolded protein response, regulates muscle differentiation. However, the role of growth arrest and DNA damage-inducible protein 34 (GADD34), one of the downstream factors of PERK, and the effects of ATRA on GADD34 expression in muscle remain unclear. In this study, we identified ATRA increased the GADD34 expression independent of the PERK signal in the gastrocnemius muscle of mice. ATRA up-regulated GADD34 expression through the transcriptional activation of gene via inhibiting the interaction of homeobox Six1 and transcription co-repressor TLE3 with the MEF3-binding site on the gene promoter in skeletal muscle. ATRA also inhibited the interaction of TTP, which induces mRNA degradation, with AU-rich element on mRNA via p-38 MAPK, resulting in the instability of mRNA. Overexpressed GADD34 in C2C12 cells changes the type of myosin heavy chain in myotubes. These results suggest ATRA increases GADD34 expression via transcriptional and post-transcriptional regulation, which changes muscle fiber type. (Keyword) Animals / Gene Expression Regulation / MAP Kinase Signaling System / Mice / Muscle Fibers, Skeletal / Protein Phosphatase 1 / RNA, Messenger / Transcription Factors / Tretinoin (Tokushima University Institutional Repository) ● Metadata: 117429 (Link to Publication Site) ● Publication site (DOI): 10.26508/lsa.202101345 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35318262 ● Search Scopus @ Elsevier (PMID): 35318262 ● Search Scopus @ Elsevier (DOI): 10.26508/lsa.202101345 (Tokushima University Institutional Repository: 117429, DOI: 10.26508/lsa.202101345, PubMed: 35318262)
9.	Kitahata Kanako, Takayuki Uchida, Taniguchi Runa, Kato Ayano, Kosuke Sugiura, Iori Sakakibara, Oarada Motoko, Tomoya Fukawa, Junsoo Park, Inho Choi and Takeshi Nikawa : Additional effects of simultaneous treatment with C14-Cblin and celastrol on the clinorotation-induced rat L6 myotube atrophy, The Journal of Medical Investigation : JMI, Vol.69, No.1,2, 127-134, 2022. (Summary) Two novel reagents, N-myristoylated Cbl-b inhibitory peptide (C14-Cblin) and celastrol, a quinone methide triterpene, are reported to be effective in preventing myotube atrophy. The combined effects of C14-Cblin and celastrol on rat L6 myotubes atrophy induced by 3D-clinorotation, a simulated microgravity model, was investigated in the present study. We first examined their effects on expression in atrogenes. Increase in MAFbx1/atrogin-1 and MuRF-1 by 3D-clinorotation was significantly suppressed by treatment with C14-Cblin or celastrol, but there was no additive effect of simultaneous treatment. However, celastrol significantly suppressed the upregulation of Cbl-b and HSP70 by 3D-clinorotation. Whereas 3D-clinorotation decreased the protein level of IRS-1 in L6 myotubes, C14-Cblin and celastrol inhibited the degradation of IRS-1. C14-Cblin and celastrol promoted the phosphorylation of FOXO3a even in microgravity condition. Simultaneous administration of C14-Cblin and celastrol had shown little additive effect in reversing the impairment of IGF-1 signaling by 3D-clinorotation. While 3D-clinorotation-induced marked oxidative stress in L6 myotubes, celastrol suppressed 3D-clinorotation-induced ROS production. Finally, the C14-Cblin and celastrol-treated groups were inhibited decrease in L6 myotube diameter and increased the protein content of slow-twitch MyHC cultured under 3D-clinorotation. The simultaneous treatment of C14-Cblin and celastrol additively prevented 3D-clinorotation-induced myotube atrophy than single treatment. J. Med. Invest. 69 : 127-134, February, 2022. (Keyword) Animals / Atrophy / Humans / Muscle Fibers, Skeletal / Pentacyclic Triterpenes / Rats / Rotation (Tokushima University Institutional Repository) ● Metadata: 116937 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.69.127 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35466134 ● Search Scopus @ Elsevier (PMID): 35466134 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.69.127 (Tokushima University Institutional Repository: 116937, DOI: 10.2152/jmi.69.127, PubMed: 35466134)
10.	Taishi Kondo, Tomoaki Ishida, Ke Ye, Marin Muraguchi, Yohei Tanimura, Masato Yoshida, Kan'ichiro Ishiuchi, Tomoki Abe, Takeshi Nikawa, Keisuke Hagihara, Hidetoshi Hayashi and Toshiaki Makino : Suppressive effects of processed aconite root on dexamethasone-induced muscle ring finger protein-1 expression and its active ingredients., Journal of Natural Medicines, Vol.76, No.3, 594-604, 2022. (Summary) Processed aconite root (PA), the tuberous root of Aconitum carmichaelii prepared by autoclaving, is a crude drug used in Japanese traditional Kampo medicine and traditional Chinese medicine for the symptoms of kidney deficiency, that is related to the muscle atrophy in modern medicine. The objective of the present study is to evaluate the effectiveness of PA on muscle atrophy and to find its active ingredients using dexamethasone-induced muscle ring finger protein-1 (MuRF1) mRNA expression in murine myoblast C2C12 cells. Dexamethasone-induced MuRF1 expression was significantly suppressed by methanol-soluble part of boiling water extract of PA in a concentration-dependent manner with its IC (Keyword) Aconitum / Animals / Dexamethasone / Mice / Muscles / Muscular Atrophy / RNA, Messenger (Link to Publication Site) ● Publication site (DOI): 10.1007/s11418-022-01606-5 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35178660 ● Search Scopus @ Elsevier (PMID): 35178660 ● Search Scopus @ Elsevier (DOI): 10.1007/s11418-022-01606-5 (DOI: 10.1007/s11418-022-01606-5, PubMed: 35178660)
11.	Madoka Kohno, ANAYT ULLA, Rina Taniguchi, Akane Ohishi, Kako Hirayama, Yuma Takemura, Shoichiro Takao, Yuki Kanazawa, Yuki Matsumoto, Masafumi Harada, Tomoya Fukawa, Hiro-omi Kanayama, Takayuki Uchida, Toshio Suzuki and Takeshi Nikawa : Daily Dietary Supplementation with Steamed Soybean Improves Muscle Volume and Strength in Healthy People Lacking Exercise., Journal of Nutritional Science and Vitaminology, Vol.68, No.6, 521-526, 2022. (Summary) Various dietary protein supplements are used by the elderly and bedridden to maintain their skeletal muscle mass and functions. High-quality proteins act as an anabolic driver and help to improve muscle strength and performance. Previously, we reported that soy protein significantly attenuates denervation-induced loss of muscle mass and myofiber cross sectional area in mice with inhibition of ubiquitination and degradation of IRS-1 in tibialis anterior muscle. It also increased muscle volume and strength in bedridden patients. In the present study, we investigated the effects of dietary soybean supplementation on muscle functions in taxi drivers lacking vigorous physical exercise. We conducted a case-control study on 25 healthy, male taxi drivers between the ages of 36 and 71 y performing minimal physical exercise. They were divided into two dietary groups: the soybean diet group (n=13) who ate daily meals (dinner) supplemented with 50 g of steamed soybean for 30 d and the control diet group (n=12) who received no soybean supplement. Next, we measured the muscle cross-sectional area (CSA) and muscle strength and function in both the groups before and after 30 d of soybean intake. The body weights of both diet groups did not differ significantly over time. However, after 30 d of soybean supplementation, the soybean-fed group developed significantly higher muscle CSA and grip strength compared to the control groups. In conclusion, dietary soybean supplementation improved muscle function in taxi drivers who lacked exercise. (Keyword) Male / Animals / Mice / Soybeans / Case-Control Studies / Muscle, Skeletal / Dietary Supplements / Muscle Strength / Dietary Proteins (Link to Publication Site) ● Publication site (DOI): 10.3177/jnsv.68.521 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36596550 ● Search Scopus @ Elsevier (PMID): 36596550 ● Search Scopus @ Elsevier (DOI): 10.3177/jnsv.68.521 (DOI: 10.3177/jnsv.68.521, PubMed: 36596550)
12.	Oarada Motoko, Yuushi Okumura, Katsuya Hirasaka, Kosuke Sugiura, Tachibana Nobuhiko, Tsurusaki Yoshinori and Takeshi Nikawa : Dietary Sodium Nitrite Causes Similar Modifications to Splenic Inflammatory Gene Expression as a High-Fat Diet, Journal of Nutritional Science and Vitaminology, Vol.67, No.6, 404-416, 2021. (Summary) Sodium nitrite (NaNO) is a widely used food additive. The present study compared the outcomes from intakes of dietary NaNO and a high-fat diet (HFD), and assessed their combined effects on inflammatory gene expression in the immune tissues of the mouse. In experiment I, mice were fed a standard low-fat diet (LFD) without or with NaNO (0.02 and 0.08%, w/w) for 11 wk. In experiment II, mice were fed an LFD without or with NaNO (0.02%) or HFD without or with NaNO (0.02%) for 11 wk. Inflammatory gene expression in the immune tissues was then measured. NaNO consumption and HFD feeding each resulted in increased splenic mRNAs for cell markers of neutrophils (Ngp, NE, Ly6g, Mpo) and eosinophils (Epo, Ear6), and an S100 family member (S100A8). In contrast, NaNO consumption and HFD feeding each resulted in decreased splenic mRNAs for cell markers of macrophages (Emr1, Itgax, CD68, CD206, Dectin-1, TLRs 4, 6, and 7), T- (CD3, CD4), NK- (CD56) and B-cells (CD20, CD40), pro- and anti-inflammatory cytokines (TNF-α, IL-6, IL-1β, IFN-γ, IL-18, IL-10, TGF-β), interleukin receptor antagonists (IL1ra, IL6ra) and cell adhesion molecules (ICAM-1, VCAM-1). However, dietary NaNO combined with HFD feeding caused no further decrease in these transcript levels compared with dietary NaNO alone. These NaNO- or HFD-induced modifications were less profound in the liver and abdominal adipose tissues than in the spleen. These findings indicate that dietary NaNO has similar modulatory effects to HFD feeding on splenic inflammatory genes. (Keyword) Animals / Diet, High-Fat / Gene Expression / Mice / Mice, Inbred C57BL / Sodium / Sodium Nitrite / Sodium, Dietary / Spleen (Link to Publication Site) ● Publication site (DOI): 10.3177/jnsv.67.404 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34980719 ● Search Scopus @ Elsevier (PMID): 34980719 ● Search Scopus @ Elsevier (DOI): 10.3177/jnsv.67.404 (DOI: 10.3177/jnsv.67.404, PubMed: 34980719)
13.	Taku Fukushima, Miho Takata, Ayano Kato, Takayuki Uchida, Takeshi Nikawa and Iori Sakakibara : Transcriptome Analyses of In Vitro Exercise Models by Clenbuterol Supplementation or Electrical Pulse Stimulation, Applied Sciences, Vol.11, No.21, 10436, 2021. (Tokushima University Institutional Repository) ● Metadata: 117280 (Link to Publication Site) ● Publication site (DOI): 10.3390/app112110436 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.3390/app112110436 (Tokushima University Institutional Repository: 117280, DOI: 10.3390/app112110436)
14.	Reiko Nakao, Shen Weilin, Shimajiri Yasuka, Kainou Kumiko, Sato Yuki, Ulla Anayt, Kohta Ohnishi, Ninomiya Miyuki, Ohno Ayako, Takayuki Uchida, Tanaka Mitsuru, Akama Kazuhito, Matsui Toshiro and Takeshi Nikawa : Oral intake of rice overexpressing ubiquitin ligase inhibitory pentapeptide prevents atrophy in denervated skeletal muscle, NPJ Science of Food, Vol.5, No.1, 25, 2021. (Summary) We previously reported that intramuscular injections of ubiquitin ligase CBLB inhibitory pentapeptide (Cblin; Asp-Gly-pTyr-Met-Pro) restored lost muscle mass caused by sciatic denervation. Here, we detected Cblin on the basolateral side of Caco-2 cells after being placed on the apical side, and found that cytochalasin D, a tight junction opener, enhanced Cblin transport. Orally administered Cblin was found in rat plasma, indicating that intact Cblin was absorbed in vitro and in vivo. Furthermore, transgenic Cblin peptide-enriched rice (CbR) prevented the denervation-induced loss of muscle mass and the upregulation of muscle atrophy-related ubiquitin ligases in mice. These findings indicated that CbR could serve as an alternative treatment for muscle atrophy. (Tokushima University Institutional Repository) ● Metadata: 117588 (Link to Publication Site) ● Publication site (DOI): 10.1038/s41538-021-00108-0 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34504092 ● Search Scopus @ Elsevier (PMID): 34504092 ● Search Scopus @ Elsevier (DOI): 10.1038/s41538-021-00108-0 (Tokushima University Institutional Repository: 117588, DOI: 10.1038/s41538-021-00108-0, PubMed: 34504092)
15.	Kiminori Yukata, Takeshi Nikawa, Mitsuhiko Takahashi and Natsuo Yasui : Overexpressed osteoactivin reduced osteoclastic callus resorption during distraction osteogenesis in mice, Journal of Pediatric Orthopaedics. Part B, Vol.30, No.5, 500-506, 2021. (Summary) Distraction osteogenesis is a widely used surgical technique to treat bone deformity and shortening. Several biological treatments have been studied to enhance bone formation during distraction osteogenesis in animals. However, role of osteoactivin in the osseous tissues during distraction osteogenesis remains poorly understood. In this animal experimental study, we investigated the spatiotemporal expression of osteoactivin by immunohistochemistry and real-time PCR using a mouse model for tibial lengthening. Furthermore, to address the role of osteoactivin in bone lengthening, we subjected the osteoactivin-transgenic mice to distraction osteogenesis model. During the lag phase, the fibroblast-like cells (possible progenitors of the osteoblasts or chondrocytes), which mainly express osteoactivin, were infiltrated into the osteotomy site. Osteoactivin was ubiquitously expressed in the lengthened segment during the distraction and consolidation phases. Consistent with the immunohistochemical analysis, the levels of the osteoactivin transcripts in the tibias were significantly increased throughout the distraction osteogenesis process. The bone mineral content in the osteoactivin-transgenic mice calculated using peripheral quantitative computed tomography was also significantly increased at the remodeling zone. The histomorphometric analysis revealed that newly formed callus resorption in the remodeling zone was significantly reduced but bone formation was not altered in the osteoactivin-transgenic mice. We conclude that osteoactivin functions as an inhibitor of callus resorption during the consolidation phase of distraction osteogenesis. (Keyword) Animals / Bone Resorption / Bone and Bones / Eye Proteins / Membrane Glycoproteins / Mice / Mice, Transgenic / Osteogenesis, Distraction / Osteotomy / Tibia (Link to Publication Site) ● Publication site (DOI): 10.1097/BPB.0000000000000789 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32732799 ● Search Scopus @ Elsevier (PMID): 32732799 ● Search Scopus @ Elsevier (DOI): 10.1097/BPB.0000000000000789 (DOI: 10.1097/BPB.0000000000000789, PubMed: 32732799)
16.	Kosuke Sugiura, Katsuya Hirasaka, Tasuku Maeda, Takayuki Uchida, Koji Kishimoto, Motoko Oarada, Siegfried Labeit, Anayt Ulla, Iori Sakakibara, Reiko Nakao, Koichi Sairyo and Takeshi Nikawa : MuRF1 deficiency prevents age-related fat weight gain, possibly through accumulation of PDK4 in skeletal muscle mitochondria in older mice, Journal of Orthopaedic Research, Vol.40, No.5, 1026-1038, 2021. (Tokushima University Institutional Repository) ● Metadata: 116581 (Link to Publication Site) ● Publication site (DOI): 10.1002/jor.25131 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34185335 ● Summary page in Scopus @ Elsevier: 2-s2.0-85109422486 (Tokushima University Institutional Repository: 116581, DOI: 10.1002/jor.25131, PubMed: 34185335, Elsevier: Scopus)
17.	Kazuhito Akama, Yasuka Shimajiri, Kumiko Kainou, Ryota Iwasaki, Reiko Nakao, Takeshi Nikawa and Akio Nishikawa : Functional rice with tandemly repeated Cbl-b ubiquitin ligase inhibitory pentapeptide prevents denervation-induced muscle atrophy in vivo, Bioscience, Biotechnology, and Biochemistry, Vol.85, No.6, 1415-1421, 2021. (Summary) Ubiquitin ligase Casitas B-lineage lymphoma-b (Cbl-b) play a critical role in nonloading-mediated skeletal muscle atrophy: Cbl-b ubiquitinates insulin receptor substrate-1 (IRS-1), leading to its degradation and a resulting loss in muscle mass. We reported that intramuscular injection of a pentapeptide, DGpYMP, which acts as a mimic of the phosphorylation site in IRS-1, significantly inhibited denervation-induced skeletal muscle loss. In order to explore the possibility of the prevention of muscle atrophy by diet therapy, we examined the effects of oral administration of transgenic rice containing Cblin (Cbl-b inhibitor) peptide (DGYMP) on denervation-induced muscle mass loss in frogs. We generated transgenic rice seeds in which 15 repeats of Cblin peptides with a WQ spacer were inserted into the rice storage protein glutelin. A diet of the transgenic rice seeds had significant inhibitory effects on denervation-induced atrophy of the leg skeletal muscles in frogs, compared with those receiving a diet of wild-type rice. (Keyword) Animals / Denervation / Enzyme Inhibitors / Mice / Muscular Atrophy / Oryza / Plants, Genetically Modified / Proto-Oncogene Proteins c-cbl / Tandem Repeat Sequences (Link to Publication Site) ● Publication site (DOI): 10.1093/bbb/zbab059 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33864463 ● Summary page in Scopus @ Elsevier: 2-s2.0-85107090566 (DOI: 10.1093/bbb/zbab059, PubMed: 33864463, Elsevier: Scopus)
18.	Ulla Anayt, Takayuki Uchida, Miki Yukari, Kosuke Sugiura, Higashitani Atsushi, Kobayashi Takeshi, Ohno Ayako, Reiko Nakao, Katsuya Hirasaka, Iori Sakakibara and Takeshi Nikawa : Morin attenuates dexamethasone-mediated oxidative stress and atrophy in mouse C2C12 skeletal myotubes, Archives of Biochemistry and Biophysics, Vol.704, 108873, 2021. (Summary) Glucocorticoids are the drugs most commonly used to manage inflammatory diseases. However, they are prone to inducing muscle atrophy by increasing muscle proteolysis and decreasing protein synthesis. Various studies have demonstrated that antioxidants can mitigate glucocorticoid-induced skeletal muscle atrophy. Here, we investigated the effect of a potent antioxidative natural flavonoid, morin, on the muscle atrophy and oxidative stress induced by dexamethasone (Dex) using mouse C2C12 skeletal myotubes. Dex (10 μM) enhanced the production of reactive oxygen species (ROS) in C2C12 myotubes via glucocorticoid receptor. Moreover, Dex administration reduced the diameter and expression levels of the myosin heavy chain protein in C2C12 myotubes, together with the upregulation of muscle atrophy-associated ubiquitin ligases, such as muscle atrophy F-box protein 1/atrogin-1, muscle ring finger protein-1, and casitas B-lineage lymphoma proto-oncogene-b. Dex also significantly decreased phosphorylated Foxo3a and increased total Foxo3a expression. Interestingly, Dex-induced ROS accumulation and Foxo3a expression were inhibited by morin (10 μM) pretreatment. Morin also prevented the Dex-induced reduction of myotube thickness, together with muscle protein degradation and suppression of the upregulation of atrophy-associated ubiquitin ligases. In conclusion, our results suggest that morin effectively prevents glucocorticoid-induced muscle atrophy by reducing oxidative stress. (Keyword) Animals / Cell Line / Dexamethasone / Dose-Response Relationship, Drug / Flavonoids / Mice / Muscle Fibers, Skeletal / Muscle Proteins / Muscular Atrophy / Oxidative Stress (Tokushima University Institutional Repository) ● Metadata: 116344 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.abb.2021.108873 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33848514 ● Search Scopus @ Elsevier (PMID): 33848514 ● Search Scopus @ Elsevier (DOI): 10.1016/j.abb.2021.108873 (Tokushima University Institutional Repository: 116344, DOI: 10.1016/j.abb.2021.108873, PubMed: 33848514)
19.	Sun Luchuanyang, Miyaji Nobuyuki, Yang Min, Mills M Edward, Taniyama Shigeto, Takayuki Uchida, Takeshi Nikawa, Li Jifeng, Shi Jie, Tachibana Katsuyasu and Katsuya Hirasaka : Astaxanthin Prevents Atrophy in Slow Muscle Fibers by Inhibiting Mitochondrial Reactive Oxygen Species via a Mitochondria-Mediated Apoptosis Pathway, Nutrients, Vol.13, No.379, 2021. (Summary) Astaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in the lipid bilayer. This study aimed to investigate the effects of AX on muscle-atrophy-mediated disturbance of mitochondria, which have a lipid bilayer. Tail suspension was used to establish a muscle-atrophied mouse model. AX diet fed to tail-suspension mice prevented loss of muscle weight, inhibited the decrease of myofiber size, and restrained the increase of hydrogen peroxide (HO) production in the soleus muscle. Additionally, AX improved downregulation of mitochondrial respiratory chain complexes I and III in the soleus muscle after tail suspension. Meanwhile, AX promoted mitochondrial biogenesis by upregulating the expressions of , , in the soleus muscle of tail-suspension mice. To confirm the AX phenotype in the soleus muscle, we examined its effects on mitochondria using Sol8 myotubes derived from the soleus muscle. We found that AX was preferentially detected in the mitochondrial fraction; it significantly suppressed mitochondrial reactive oxygen species (ROS) production in Sol8 myotubes. Moreover, AX inhibited the activation of caspase 3 via inhibiting the release of cytochrome c into the cytosol in antimycin A-treated Sol8 myotubes. These results suggested that AX protected the functional stability of mitochondria, alleviated mitochondrial oxidative stress and mitochondria-mediated apoptosis, and thus, prevented muscle atrophy. (Keyword) astaxanthin / mitochondria / muscle atrophy / oxidative stress (Tokushima University Institutional Repository) ● Metadata: 116285 (Link to Publication Site) ● Publication site (DOI): 10.3390/nu13020379 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33530505 ● Summary page in Scopus @ Elsevier: 2-s2.0-85099928726 (Tokushima University Institutional Repository: 116285, DOI: 10.3390/nu13020379, PubMed: 33530505, Elsevier: Scopus)
20.	Rie Mukai, Takashi Fukuda, Asami Ohnishi, Takeshi Nikawa, Mutsuki Furusawa and Junji Terao : Chocolate as a food matrix reduces the bioavailability of galloylated catechins from green tea in healthy women., Food & Function, Vol.12, No.1, 408-416, 2021. (Summary) In this study, we evaluated the food matrix effects of chocolate on the absorption of green tea catechins (GTCs), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), and (-)-epigallocatechin gallate (EGCg), in five healthy 22-year-old women. In the single-intake experiment, the plasma concentrations of ECg (P < 0.05, at 1.5 h) and EGCg (P < 0.05, at 6 h) but not those of EC and EGC were reduced by the chocolate matrix. Regardless of the chocolate matrix, ECg and EGCg were mainly present as their aglycones in the plasma, whereas EGC and EC were found mostly as conjugated metabolites. After daily intake of GTCs mixed with chocolate for 14 days followed by overnight fasting, ECg but not EGCg was detected in the plasma. To compare the plasma profiles of ECg and EGCg, a mixture containing approximately equal amounts of ECg and EGCg was administered to nine rats for 14 days. Following treatment and overnight food deprivation, the plasma content of ECg was higher than that of EGCg. After a single injection of the same mixture in seven rats, ECg levels were higher than those of EGCg, and a greater amount of conjugated metabolites of ECg than those of EGCg was detected in the plasma 10 h after administration. In conclusion, the chocolate matrix affects the plasma profiles of GTCs, particularly ECg. ECg appears to persist in the plasma for a longer period, regardless of the chocolate matrix. (Keyword) Adult / Animals / Biological Availability / Catechin / Chocolate / Female / Food / Humans / Male / Models, Animal / Rats / Rats, Wistar / Reference Values / Tea / Young Adult (Tokushima University Institutional Repository) ● Metadata: 115529 (Link to Publication Site) ● Publication site (DOI): 10.1039/d0fo02485f (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33393957 ● Search Scopus @ Elsevier (PMID): 33393957 ● Search Scopus @ Elsevier (DOI): 10.1039/d0fo02485f (Tokushima University Institutional Repository: 115529, DOI: 10.1039/d0fo02485f, PubMed: 33393957)
21.	Ohno Ayako, Nobuo Maita, Tabata Takanori, Nagano Hikaru, Arita Kyohei, Ariyoshi Mariko, Takayuki Uchida, Reiko Nakao, Ulla Anayt, Kosuke Sugiura, Koji Kishimoto, Teshima-Kondo Shigetada, Okumura Yuushi and Takeshi Nikawa : Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza., Life Science Alliance, Vol.4, No.6, e202000849, 2021. (Summary) Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19. (Keyword) Animals / Birds / Crystallography, X-Ray / Humans / Influenza in Birds / Membrane Proteins / Orthomyxoviridae / Protein Conformation / Serine Endopeptidases (Tokushima University Institutional Repository) ● Metadata: 116821 (Link to Publication Site) ● Publication site (DOI): 10.26508/LSA.202000849 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33820827 ● Summary page in Scopus @ Elsevier: 2-s2.0-85103997820 (Tokushima University Institutional Repository: 116821, DOI: 10.26508/LSA.202000849, PubMed: 33820827, Elsevier: Scopus)
22.	Takeshi Nikawa and Kazumi Ishidoh : Ubiquitin ligase Cbl-b and inhibitory Cblin peptides, Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol.1868, No.11, 140495, 2020. (Summary) This review focuses on the Cbl-b muscle atrophy-associated ubiquitin ligase and its inhibitors. Herein, the role of E3 ubiquitin ligase-associated muscle atrophy genes (atrogenes), including MAFbx-1/agrogin-1 and MuRF-1, as well as another ubiquitin ligase, Cbl-b and its inhibitors, is discussed. Cbl-b plays an important role in unloading muscle atrophy caused by spaceflight and in bedridden patients: Cbl-b ubiquitinated and induced the degradation of IRS-1, a key intermediate in the IGF-1 signaling. Furthermore, a pentapetpide (DGpYMP), inhibited Cbl-b-mediated IRS-1 ubiquitination. This peptide-based Cbl-b inhibitor Cblin and its homologous peptides in foods presumably affect muscle atrophy under such conditions. (Keyword) Adaptor Proteins, Signal Transducing / Animals / Humans / Muscular Atrophy / Oligopeptides / Proto-Oncogene Proteins c-cbl / Ubiquitination (Tokushima University Institutional Repository) ● Metadata: 116485 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbapap.2020.140495 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32663526 ● Search Scopus @ Elsevier (PMID): 32663526 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbapap.2020.140495 (Tokushima University Institutional Repository: 116485, DOI: 10.1016/j.bbapap.2020.140495, PubMed: 32663526)
23.	Luqman Khan, Katsumi Sato, Shinichi okuyama, Takeshi Kobayashi, Kazumasa Ohashi, Katsuya Hirasaka, Takeshi Nikawa, Kunio Takada, Atsushi Higashitani and Kenji Abiko : Ultra-high-purity iron is a novel and very compatible biomaterial, Journal of the Mechanical Behavior of Biomedical Materials, Vol.106, 103744, 2020. (Summary) Metals and alloys are used widely in bone prosthetic materials, stents and dental tissue reconstructions. The most common materials are stainless steels and cobalt-chromium-nickel and titanium alloys. These alloys can be easily deformed but are hard to break. However, their affinity for cells and tissues is very low. In addition, they can sometimes provoke unexpected metal allergies. Iron is an abundant trace element essential for humans. However, excess amounts in particular of Fe ions are toxic. We previously succeeded in obtaining 99.9996% ultra-high-purity iron (ABIKO iron). The chemical properties of ABIKO iron are completely different from that of conventional pure iron. For example, the reaction rate in hydrochloric acid is very slow and there is barely any corrosion. Here, we found that, in the absence of any type of coating, mammalian cells could easily attach to, and normally proliferate and differentiate on, ABIKO iron. On the other hand, cell densities and proliferation rate of the surfaces of plates made from Co-Cr-Mo or Ti-6Al-4V were significantly reduced. In addition, several stress and iron response genes, HSP70, SOD1, ATM and IRP2 did not change in the cells on ABIKO iron, while these genes were induced with exogenous application of FeSO. Cells also secreted and fastened some organics on ABIKO iron. In vitro collagen binding assay showed that ABIKO iron binds higher amount of collagens. These findings highlight ABIKO iron as a novel biocompatible prosthetic material. (Keyword) Alloys / Animals / Biocompatible Materials / Cobalt / Corrosion / Humans / Iron / Materials Testing / Titanium (Tokushima University Institutional Repository) ● Metadata: 116558 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jmbbm.2020.103744 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32250954 ● Search Scopus @ Elsevier (PMID): 32250954 ● Search Scopus @ Elsevier (DOI): 10.1016/j.jmbbm.2020.103744 (Tokushima University Institutional Repository: 116558, DOI: 10.1016/j.jmbbm.2020.103744, PubMed: 32250954)
24.	Nobuhiko Tachibana, Masanori Fukao, Tomoko Irie, Yusuke Irisawa, Hirotaka Shirono, Motoko Oarada, Takeshi Nikawa and Tetsuya Fukaya : A Diet Including Red Bell Pepper Juice and Soy Protein Suppress Physiological Markers of Muscle Atrophy in Mice, Journal of Nutritional Science and Vitaminology, Vol.66, No.5, 449-455, 2020. (Link to Publication Site) ● Publication site (DOI): 10.3177/jnsv.66.449 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33132348 ● Search Scopus @ Elsevier (PMID): 33132348 ● Search Scopus @ Elsevier (DOI): 10.3177/jnsv.66.449 (DOI: 10.3177/jnsv.66.449, PubMed: 33132348)
25.	Yuki Niida, Masashi Masuda, Yuichiro Adachi, Aika Yoshizawa, Hirokazu Ohminami, Yuki Mori, Kohta Ohnishi, Hisami Okumura, Takayuki Uchida, Takeshi Nikawa, Hironori Yamamoto, Makoto Miyazaki and Yutaka Taketani : Reduction of stearoyl-CoA desaturase (SCD) contributes muscle atrophy through the excess endoplasmic reticulum stress in chronic kidney disease, Journal of Clinical Biochemistry and Nutrition, Vol.67, No.2, 179-187, 2020. (Summary) <p>Skeletal muscle atrophy is associated with mortality and poor prognosis in patients with chronic kidney disease (CKD). However, underlying mechanism by which CKD causes muscle atrophy has not been completely understood. The quality of lipids (lipoquality), which is defined as the functional features of diverse lipid species, has recently been recognized as the pathology of various diseases. In this study, we investigated the roles of the stearoyl-CoA desaturase (SCD), which catalyzes the conversion of saturated fatty acids into monounsaturated fatty acids, in skeletal muscle on muscle atrophy in CKD model animals. In comparison to control rats, CKD rats decreased the SCD activity and its gene expression in atrophic gastrocnemius muscle. Next, oleic acid blocked the reduction of the thickness of C2C12 myotubes and the increase of the endoplasmic reticulum stress induced by SCD inhibitor. Furthermore, endoplasmic reticulum stress inhibitor ameliorated CKD-induced muscle atrophy (the weakness of grip strength and the decrease of muscle fiber size of gastrocnemius muscle) in mice and the reduction of the thickness of C2C12 myotubes by SCD inhibitor. These results suggest that the repression of SCD activity causes muscle atrophy through excessive endoplasmic reticulum stress in CKD.</p> (Keyword) skeletal muscle atrophy / endoplasmic reticulum stress / chronic kidney disease / stearoyl-CoA desaturase / saturated fatty acid (Tokushima University Institutional Repository) ● Metadata: 114720 (Link to Publication Site) ● Publication site (DOI): 10.3164/jcbn.20-24 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33041516 ● CiNii @ National Institute of Informatics (CRID): 1390566775163696384 ● Search Scopus @ Elsevier (PMID): 33041516 ● Search Scopus @ Elsevier (DOI): 10.3164/jcbn.20-24 (Tokushima University Institutional Repository: 114720, DOI: 10.3164/jcbn.20-24, PubMed: 33041516, CiNii: 1390566775163696384)
26.	Kanae Saitoh, Tomohiro Yoshimura1, Luchuanyang Sun, Min Yang, Yao Wang, Shigeto Taniyama, Kenji Hara, Fumihito Murayama, Takeshi Nikawa, Katsuyasu Tachibana and Katsuya Hirasaka : Effect of dietary fish oil on enhanced inflammation and disturbed lipophagy in white adipose tissue caused by a high fat diet., Fisheries Science, Vol.86, No.1, 187-196, 2020. (Link to Publication Site) ● Publication site (DOI): 10.1007/s12562-019-01374-4 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-85074710850 (DOI: 10.1007/s12562-019-01374-4, Elsevier: Scopus)
27.	Tomohiro Yoshimura, Kanae Saitoh, Luchuanyang Sun, Yao Wang, Shigeto Taniyama, Kenichi Yamaguchi, Takayuki Uchida, Tsutomu Ohkubo, Atsushi Higashitani, Takeshi Nikawa, Katsuyasu Tachibana and Katsuya Hirasaka : Morin suppresses cachexia-induced muscle wasting by binding to ribosomal protein S10 in carcinoma cells., Biochemical and Biophysical Research Communications, Vol.506, No.4, 773-779, 2018. (Summary) Cachexia, observed in most cancer patients, is a syndrome that includes wasting of bodily energy reserves and is characterized by muscle atrophy and fat loss. We have previously demonstrated that isoflavones, such as genistein and daidzein, prevent muscle wasting in tumor-bearing mice. In this study, we examined the effect of morin, a flavonoid, on cachexia. The wet weight and myofiber size of muscles in Lewis lung carcinoma (LLC) cell-bearing mice fed a normal diet were decreased, compared with those in control mice fed a normal diet. In contrast, intake of morin prevented the reduction of muscle wet weight and myofiber size. Moreover, the tumor weight in mice fed the morin diet was lower than that in mice fed the normal diet. Both cell viability and protein synthetic ability of LLC cells were reduced by treatment with morin, but C2C12 myotubes were not affected. Binding assay using morin-conjugated magnetic beads identified ribosomal protein S10 (RPS10) as a target protein of morin. Consistent with the result of morin treatment, knockdown of RPS10 suppressed LLC cell viability. These results suggest that morin indirectly prevents muscle wasting induced by cancer cachexia by suppressing cancer growth via binding to RPS10. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2018.10.184 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30389140 ● Summary page in Scopus @ Elsevier: 2-s2.0-85056802520 (DOI: 10.1016/j.bbrc.2018.10.184, PubMed: 30389140, Elsevier: Scopus)
28.	Shigeru Hiramoto, Nobuhiro Yahata, Kanae Saitoh, Tomohiro Yoshimura, Yao Wang, Shigeto Taniyama, Takeshi Nikawa, Katsuyasu Tachibana and Katsuya Hirasaka : Dietary supplementation with alkylresorcinols prevents muscle atrophy through a shift of energy supply., The Journal of Nutritional Biochemistry, Vol.61, 147-154, 2018. (Summary) It has been reported that phytoextracts that contain alkylresorcinols (ARs) protect against severe myofibrillar degeneration found in isoproterenol-induced myocardial infarction. In this study, we examined the effect of dietary ARs derived from wheat bran extracts on muscle atrophy in denervated mice. The mice were divided into the following four groups: (1) sham-operated (control) mice fed with normal diet (S-ND), (2) denervated mice fed with normal diet (D-ND), (3) control mice fed with ARs-supplemented diet (S-AR) and (4) denervated mice fed with ARs-supplemented diet (D-AR). The intake of ARs prevented the denervation-induced reduction of the weight of the hind limb muscles and the myofiber size. However, the expression of ubiquitin ligases and autophagy-related genes, which is associated with muscle proteolysis, was slightly higher in D-AR than in D-ND. Moreover, the abundance of the autophagy marker p62 was significantly higher in D-AR than in D-ND. Muscle atrophy has been known to be associated with a disturbed energy metabolism. The expression of pyruvate dehydrogenase kinase 4 (PDK4), which is related to fatty acid metabolism, was decreased in D-ND as compared with that in S-ND. In contrast, dietary supplementation with ARs inhibited the decrease of PDK4 expression caused by denervation. Furthermore, the abnormal expression pattern of genes related to the abundance of lipid droplets-coated proteins that was induced by denervation was improved by ARs. These results raise the possibility that dietary supplementation with ARs modifies the disruption of fatty acid metabolism induced by lipid autophagy, resulting in the prevention of muscle atrophy. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jnutbio.2018.08.014 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30236871 ● Search Scopus @ Elsevier (PMID): 30236871 ● Search Scopus @ Elsevier (DOI): 10.1016/j.jnutbio.2018.08.014 (DOI: 10.1016/j.jnutbio.2018.08.014, PubMed: 30236871)
29.	Chisato Tomida, Naoko Yakagishi, Hikaru Nagano, Takayuki Uchida, Ayako Maita, Katsuya Hirasaka, Takeshi Nikawa and Shigetada Kondo : VEGF pathway-targeting drugs induce evasive adaptation by activation of neuropilin-1/cMet in colon cancer cells., International Journal of Oncology, Vol.52, No.4, 1350-1362, 2018. (Summary) Anti-angiogenic therapies targeting vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) are important treatments for a number of human malignancies, including colorectal cancers. However, there is increasing evidence that VEGF/VEGF-R inhibitors promote the adaptive and evasive resistance of tumor cells to the therapies. The mechanism by which the cancer cells become resistant remains unclear. One potential mechanism is that VEGF/VEGF-R blockers directly act on tumor cells independently of anti-angiogenic effects. In this study, the direct effects of an anti-VEGF antibody (bevacizumab) and a VEGF-R tyrosine kinase inhibitor (sunitinib) on the evasive adaptation of colon cancer cells were compared. HCT116 and RKO human colon cancer cell lines were chronically exposed (3 months) to bevacizumab or sunitinib in vitro to establish bevacizumab- and sunitinib-adapted cells, respectively. Transwell migration and invasion assays, western blotting, reverse transcription-quantitative polymerase chain reaction, co-immunoprecipitation analysis, cell survival assays and ELISAs were conducted to analyze the adapted cells. Compared with the control vehicle-treated cells, the two cell models exhibited increased migration and invasion activities to different degrees and through different mechanisms. The bevacizumab-adapted cells, but not in the sunitinib-adapted cells, exhibited redundantly increased expression levels of VEGF/VEGF-R family members, including VEGF-A, placental growth factor, VEGF-C, VEGF-R1 and VEGF-R3. In addition, the phosphorylation levels of VEGF-R1 and VEGF-R3 were increased in the bevacizumab-adapted cells compared with the control cells. Thus, the inhibition of VEGF-R1 and VEGF-R3 decreased the evasive activities of the cells, suggesting that they remained dependent on redundant VEGF/VEGF-R signaling. By contrast, the sunitinib-adapted cells exhibited increased neuropilin-1 (NRP1) expression levels compared with the control cells. In the sunitinib-adapted cells, NRP1 interacted with phosphorylated cMet, and the cMet activation was dependent on NRP1. Thus, NRP1 or cMet blockade suppressed the evasive activation of the sunitinib-adapted cells. These results suggest that the sunitinib-adapted cells switched from a VEGF-R-dependent pathway to an alternative NRP1/cMet-dependent one. The findings of the present study indicate that VEGF/VEGF-R inhibitors directly act on colon cancer cells and activate their evasive adaptation via different mechanisms. (Tokushima University Institutional Repository) ● Metadata: 111606 (Link to Publication Site) ● Publication site (DOI): 10.3892/ijo.2018.4291 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29532881 ● Summary page in Scopus @ Elsevier: 2-s2.0-85042801496 (Tokushima University Institutional Repository: 111606, DOI: 10.3892/ijo.2018.4291, PubMed: 29532881, Elsevier: Scopus)
30.	Takayuki Uchida, Yoshihiro Sakashita, Kanako Kitahata, Yui Yamashita, Chisato Tomida, Yuki Kimori, Akio Komatsu, Katsuya Hirasaka, Ayako Maita, Reiko Nakao, Atsushi Higashitani, Akira Higashibata, Noriaki Ishioka, Toru Shimazu, Takeshi Kobayashi, Yuushi Okumura, Inho Choi, Motoko Oarada, M Edward Mills, Shigetada Kondo, Shin'ichi Takeda, Eiji Tanaka, Keiji Tanaka, Masahiro Sokabe and Takeshi Nikawa : Reactive oxygen species up-regulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells., American Journal of Physiology, Cell Physiology, Vol.314, No.6, C721-C731, 2018. (Summary) Unloading-mediated muscle atrophy is associated with increased reactive oxygen species (ROS) production. We previously demonstrated that elevated ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) resulted in the loss of muscle volume [Nakao R. et al. Mol Cell Biol, 29: 4798-4811, 2009]. However, the pathological role of ROS production associated with unloading-mediated muscle atrophy still remains unknown. Here, we showed the ROS-mediated signal transduction caused by microgravity or its simulation contributes to Cbl-b expression. In L6 myotubes, the assessment of redox status revealed that oxidized glutathione was increased under microgravity conditions, and simulated microgravity caused a burst of ROS, implicating ROS as a critical upstream mediator linking to downstream atrophic signaling. ROS generation activated the ERK1/2-early growth response protein (Egr) 1/2-Cbl-b signaling pathway, an established contributing pathway to muscle volume loss. Interestingly, antioxidant treatment, such as N-acetylcysteine and TEMPOL, but not catalase, blocked the clinorotation-mediated activation of ERK1/2. The increased ROS induced transcriptional activity of Egr 1 and/or Egr 2 to stimulate Cbl-b expression through the ERK 1/2 pathway in L6 myoblasts, since treatment with Egr 1/2 siRNA and an ERK 1/2 inhibitor significantly suppressed clinorotation-induced Cbl-b and Egr expression, respectively. Promoter and gel mobility shift assays revealed that Cbl-b was upregulated via an Egr consensus oxidative responsive element at -110 to -60 bp of the Cbl-b promoter. Together this indicates that under microgravity conditions, elevated ROS may be a crucial mechanotransducer in skeletal muscle cells, regulating muscle mass, through Cbl-b expression activated by the ERK-Egr signaling pathway. (Tokushima University Institutional Repository) ● Metadata: 111610 (Link to Publication Site) ● Publication site (DOI): 10.1152/ajpcell.00184.2017 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29513566 ● Search Scopus @ Elsevier (PMID): 29513566 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpcell.00184.2017 (Tokushima University Institutional Repository: 111610, DOI: 10.1152/ajpcell.00184.2017, PubMed: 29513566)
31.	Manami Abe, Yuki Matsuo, Akiko Harada, Takayuki Uchida, Kanako Kitahata, Chisato Tomida, Katsuya Hirasaka, Shigetada Kondo, Nagakatsu Harada, Yutaka Nakaya, Hiroshi Sakaue, Reiko Nakao and Takeshi Nikawa : Distinct Gene Expression Profile Distinguishes Increased Metabolic Activity in Spontaneously Hyperactive Rats While Sedentary from That Induced by Exercise, Advances in Biological Chemistry, Vol.8, No.01, 1-14, 2018. (Tokushima University Institutional Repository) ● Metadata: 111609 (Link to Publication Site) ● Publication site (DOI): 10.4236/abc.2018.81001 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.4236/abc.2018.81001 (Tokushima University Institutional Repository: 111609, DOI: 10.4236/abc.2018.81001)
32.	ODO BAYARSAIKHAN, Nobuhiko Kawai, Hiroyo Mori, Nao Kinouchi, Takeshi Nikawa and Eiji Tanaka : Effects of co-transfection with myostatin-targeting siRNA and ActRIIB-Fc fusion proein on skeletal muscle growth., Journal of Oral Health and Biosciences, Vol.30, No.1, 1-7, 2017. (Tokushima University Institutional Repository) ● Metadata: 111062 (Link to Publication Site) ● Publication site (DOI): 10.20738/johb.30.1_1 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.20738/johb.30.1_1 (Tokushima University Institutional Repository: 111062, DOI: 10.20738/johb.30.1_1)
33.	Hidehiro Umehara, Shusuke Numata, Shinya Watanabe, Yutaka Hatakeyama, Makoto Kinoshita, Yukiko Tomioka, Kiyoshi Nakahara, Takeshi Nikawa and Tetsuro Ohmori : Altered KYN/TRP, Gln/Glu, and Met/methionine sulfoxide ratios in the blood plasma of medication-free patients with major depressive disorder., Scientific Reports, Vol.7, No.1, 4855, 2017. (Summary) Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) is a comprehensive, quantitative, and high throughput tool used to analyze metabolite profiles. In the present study, we used CE-TOFMS to profile metabolites found in the blood plasma of 33 medication-free patients with major depressive disorder (MDD) and 33 non-psychiatric control subjects. We then investigated changes which occurred in the metabolite levels during an 8-week treatment period. The medication-free MDD patients and control subjects showed significant differences in their mean levels of 33 metabolites, including kynurenine (KYN), glutamate (Glu), glutamine (Gln), methionine sulfoxide, and methionine (Met). In particular, the ratios of KYN to tryptophan (TRP), Gln to Glu, and Met to methionine sulfoxide were all significantly different between the two groups. Among the 33 metabolites with altered levels in MDD patients, the levels of KYN and Gln, as well as the ratio of Gln to Glu, were significantly normalized after treatment. Our findings suggest that imbalances in specific metabolite levels may be involved in the pathogenesis of MDD, and provide insight into the mechanisms by which antidepressant agents work in MDD patients. (Tokushima University Institutional Repository) ● Metadata: 110182 (Link to Publication Site) ● Publication site (DOI): 10.1038/s41598-017-05121-6 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28687801 ● Search Scopus @ Elsevier (PMID): 28687801 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-017-05121-6 (Tokushima University Institutional Repository: 110182, DOI: 10.1038/s41598-017-05121-6, PubMed: 28687801)
34.	Hyunwoo Ju, Taewan Kim, Chan-Moon Chung, Junsoo Park, Takeshi Nikawa, Kyoungsook Park and Inho Choi : Metabolic Suppression by 3-Iodothyronamine Induced Muscle Cell Atrophy via Activation of FoxO-Proteasome Signaling and Downregulation of Akt1-S6K Signaling., Biological & Pharmaceutical Bulletin, Vol.40, No.5, 576-582, 2017. (Summary) The homeostasis of muscle properties depends on both physical and metabolic stresses. Whereas physical stress entails metabolic response for muscle homeostasis, the latter does not necessarily involve the former and may thus solely affect the homeostasis. We here report that metabolic suppression by the hypometabolic agent 3-iodothyronamine (T1AM) induced muscle cell atrophy without physical stress. We observed that the oxygen consumption rate of C2C12 myotubes decreased 40% upon treatment with 75 µM T1AM for 6 h versus 10% in the vehicle (dimethyl sulfoxide) control. The T1AM treatment reduced cell diameter of myotubes by 15% compared to the control (p<0.05). The cell diameter was reversed completely by 9 h after T1AM was removed. The T1AM treatment also significantly suppressed the expression levels of heat shock protein 72 and αB-crystallin as well as the phosphorylation levels of Akt1, mammalian target of rapamycin (mTOR), S6K, forkhead box O1 (FoxO1) and FoxO3. In contrast, the levels of ubiquitin E3 ligase MuRF1 and chymotrypsin-like activity of proteasome were significantly elevated by T1AM treatment. These results suggest that T1AM-mediated metabolic suppression induced muscle cell atrophy via activation of catabolic signaling and inhibition of anabolic signaling. (Link to Publication Site) ● Publication site (DOI): 10.1248/bpb.b16-00653 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28163294 ● Search Scopus @ Elsevier (PMID): 28163294 ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b16-00653 (DOI: 10.1248/bpb.b16-00653, PubMed: 28163294)
35.	Hiroko Ikeda, Hikaru Souda, Anggraeini Puspitasari, D Kathryn Held, Jun Hidema, Takeshi Nikawa, Yukari Yoshida, Tatsuaki Kanai and Akihisa Takahashi : Development and performance evaluation of a three-dimensional clinostat synchronized heavy-ion irradiation system., Life Sciences in Space Research, Vol.12, 51-60, 2017. (Summary) Outer space is an environment characterized by microgravity and space radiation, including high-energy charged particles. Astronauts are constantly exposed to both microgravity and radiation during long-term stays in space. However, many aspects of the biological effects of combined microgravity and space radiation remain unclear. We developed a new three-dimensional (3D) clinostat synchronized heavy-ion irradiation system for use in ground-based studies of the combined exposures. Our new system uses a particle accelerator and a respiratory gating system from heavy-ion radiotherapy to irradiate samples being rotated in the 3D clinostat with carbon-ion beams only when the samples are in the horizontal position. A Peltier module and special sample holder were loaded on a static stage (standing condition) and the 3D clinostat (rotation condition) to maintain a suitable temperature under atmospheric conditions. The performance of the new device was investigated with normal human fibroblasts 1BR-hTERT in a disposable closed cell culture chamber. Live imaging revealed that cellular adhesion and growth were almost the same for the standing control sample and rotation sample over 48h. Dose flatness and symmetry were judged according to the relative density of Gafchromic films along the X-axis and Y-axis of the positions of the irradiated sample to confirm irradiation accuracy. Doses calculated using the carbon-ion calibration curve were almost the same for standing and rotation conditions, with the difference being less than 5% at 1Gy carbon-ion irradiation. Our new device can accurately synchronize carbon-ion irradiation and simulated microgravity while maintaining the temperature under atmospheric conditions at ground level. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.lssr.2017.01.003 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28212708 ● Summary page in Scopus @ Elsevier: 2-s2.0-85011362866 (DOI: 10.1016/j.lssr.2017.01.003, PubMed: 28212708, Elsevier: Scopus)
36.	Atsuko Sakai, Hisayo Hamada, Keiko Hara, Kyoko Mori, Takayuki Uchida, Takashi Mizuguchi, Jun Minaguchi, Kenji Shima, Shu Kawashima, Yasuhiro Hamada and Takeshi Nikawa : Nutritional counseling regulates interdialytic weight gain and blood pressure in outpatients receiving maintenance hemodialysis., The Journal of Medical Investigation : JMI, Vol.64, No.1,2, 129-135, 2017. (Summary) Maintenance hemodialysis outpatients must limit salt and water intake to maintain electrolyte balance and blood pressure. In Kawashima Hospital, nationally registered dietitians provide hemodialysis patients with monthly nutritional counseling. We investigated whether nutritional counseling affects interdialytic weight gain (IDWG) and blood pressure. We investigated 48 hemodialysis patients whose monthly average IDWG ratio to dry weight exceeded 5.1% and who had not had a long-term hospital admittance of > 1 month. After the 48-month nutritional counseling period, the IDWG ratio had improved in 37 of the patients (77.1%), significantly decreasing from 6.0±0.7 to 5.3±0.9%. Estimated salt and water intake decreased significantly from 13.3±2.7 to 11.8±2.4 g/day and 2528±455 to 2332±410 ml/day, respectively. During the intervention period, normalized protein catabolic rate and body mass index did not change substantially. Pre-hemodialysis systolic and diastolic blood pressures had significantly decreased from 149±19 to 134±18 mmHg, and 82±13 to 75±10 mmHg for 48 months after study initiation, respectively. The dosage of antihypertensive drugs had significantly decreased in the group that experienced improvement in the IDWG ratio. Long-term nutritional counseling by nationally registered dietitians may improve the IDWG ratio and blood pressure of hemodialysis patients by decreasing their salt and water intake. J. Med. Invest. 64: 129-135, February, 2017. (Keyword) Adult / Ambulatory Care / Antihypertensive Agents / blood pressure / counseling / Female / Humans / hypertension / Male / Middle Aged / Nutrition Therapy / Nutritional Status / Renal Dialysis / Weight Gain (Tokushima University Institutional Repository) ● Metadata: 111100 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.64.129 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28373609 ● Summary page in Scopus @ Elsevier: 2-s2.0-85016435609 (Tokushima University Institutional Repository: 111100, DOI: 10.2152/jmi.64.129, PubMed: 28373609, Elsevier: Scopus)
37.	Chisato Tomida, Hikaru Nagano, Naoko Yamagishi, Takayuki Uchida, Ayako Maita, Katsuya Hirasaka, Takeshi Nikawa and Shigetada Kondo : Regorafenib induces adaptive resistance of colorectal cancer cells via inhibition of vascular endothelial growth factor receptor., The Journal of Medical Investigation : JMI, Vol.64, No.3-4, 262-265, 2017. (Summary) Recently, inhibition of tumor angiogenesis has become an important anti-cancer therapy. Tumor angiogenesis is regulated by multiple signaling pathways, including VEGF and VEGF receptor (VEGF-R), FGF and FGF receptor (FGF-R), and PDGF and PDGF receptor (PDGF-R) pathways. Thus, the antiangiogenic agents, such as regorafenib, simultaneously target those receptors on vascular endothelial cells. In addition to endothelial cells, cancer cells express the three receptors, suggesting that the antiangiogenic inhibitors affect tumor cells. In fact, we previously demonstrated that regorafenib directly acted on human colorectal cancer cells and accelerated their apoptosis resistance and migration capability. Thus, we here elucidated how regorafenib induced the malignant phenotypes in colorectal cancer cells. To identify the responsible receptor among the regorafenib-targeting proangiogenic receptors, we examined the effects of a potent selective inhibitor for VEGF-R, FGF-R or PDGF-R on apoptosis resistance and migration capability. We clarified that blockade of VEGF-R, but not FGF-R and PDGF-R, induced the malignant phenotypes. We confirmed that blocking of VEGF ligands derived from colorectal cancer cells also induced the phenotypes. These results suggest that regorafenib progressed the malignancy via prevention of autocrine and paracrine VEGF signaling in colorectal cancer cells. J. Med. Invest. 64: 262-265, August, 2017. (Keyword) Angiogenesis Inhibitors / Apoptosis / Cell Movement / Colorectal Neoplasms / Drug Resistance, Neoplasm / HCT116 Cells / Humans / Phenylurea Compounds / Protein-Tyrosine Kinases / Pyridines / Receptors, Vascular Endothelial Growth Factor (Tokushima University Institutional Repository) ● Metadata: 111128 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.64.262 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28954993 ● CiNii @ National Institute of Informatics (CRID): 1390282679224220288 ● Summary page in Scopus @ Elsevier: 2-s2.0-85030250811 (Tokushima University Institutional Repository: 111128, DOI: 10.2152/jmi.64.262, PubMed: 28954993, CiNii: 1390282679224220288, Elsevier: Scopus)
38.	Chisato Tomida, Naoko Yamagishi, Hikaru Nagano, Takayuki Uchida, Ayako Maita, Katsuya Hirasaka, Takeshi Nikawa and Shigetada Kondo : Antiangiogenic agent sunitinib induces epithelial to mesenchymal transition and accelerates motility of colorectal cancer cells., The Journal of Medical Investigation : JMI, Vol.64, No.3-4, 250-254, 2017. (Summary) Although vascular endothelial growth factor receptor (VEGF-R)-targeted antiangiogenic agents are important treatment for a number of human malignancies, there is accumulating evidence that the therapies may promote disease progression, such as invasion and metastasis. How tumors become to promote their evasiveness remains fully uncertain. One of possible mechanisms for the adaptation may be a direct effect of VEGF-R inhibitors on tumor cells expressing VEGF-R. To elucidate a direct effect of VEGF-R-targeting drug (sunitinib), we established a human colorectal cancer cell model adapted to sunitinib. The sunitinib-conditioned cells showed a significant increase in cellular motility and migration activities, compared to the vehicle-treated control cells. Consistent with the phenotype, the sunitinib-conditioned cells decreased the expression levels of E-cadherin (an epithelial marker), while significantly increased the levels of Slug and Zeb1 (mesenchymal markers). Expression profiles of VEGF-R in the sunitinib-conditioned cells showed that only neuropilin-1 (NRP1) expression was significantly increased among all VEGF-R tested. Blockade of NRP1 using its antagonist clearly repressed the migration activation in sunitinib-conditioned cells, but not in the control cells. These results suggest that inhibition of VEGF-R on colorectal cancer cells can drive the epithelial-mesenchymal transition, leading to activation of cell motility in an NRP1-dependent manner. J. Med. Invest. 64: 250-254, August, 2017. (Keyword) Angiogenesis Inhibitors / Cell Movement / Colorectal Neoplasms / Epithelial-Mesenchymal Transition / HCT116 Cells / Humans / Indoles / Neuropilin-1 / Pyrroles / Receptors, Vascular Endothelial Growth Factor / Transcriptome (Tokushima University Institutional Repository) ● Metadata: 111126 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.64.250 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28954991 ● CiNii @ National Institute of Informatics (CRID): 1390001204247522048 ● Summary page in Scopus @ Elsevier: 2-s2.0-85030217718 (Tokushima University Institutional Repository: 111126, DOI: 10.2152/jmi.64.250, PubMed: 28954991, CiNii: 1390001204247522048, Elsevier: Scopus)
39.	ODO BAYARSAIKHAN, Nobuhiko Kawai, Hiroyo Mori, Nao Kinouchi, Takeshi Nikawa and Eiji Tanaka : Co-Administration of Myostatin-Targeting siRNA and ActRIIB-Fc Fusion Protein Increases Masseter Muscle Mass and Fiber Size., Journal of Nutritional Science and Vitaminology, Vol.63, No.4, 244-248, 2017. (Summary) Myostatin, a member of the TGF- superfamily, is a negative regulator of skeletal muscle cell growth and differentiation, and binds with high affinity to the activin type IIB receptor (ActRIIB). The soluble ligand-binding domain of ActRIIB fused to the Fc domain of IgG (ActRIIB-Fc) potently binds and inhibits TGF- family members in muscle, leading to rapid and marked muscle growth. The present study was designed to assess the effectiveness of the co-delivery of myostatin-targeting siRNA (Mstn-siRNA) and ActRIIB-Fc into skeletal muscle as a potential treatment of atrophic myopathies. Eleven-week-old, male C57BL/6 mice were injected with atelocollagen (ATCOL)-mediated Mstn-siRNA with/without ActRIIB-Fc locally into the masseter muscle twice a week. Inhibition of myostatin function by the combination of Mstn-siRNA and ActRIIB-Fc increased muscle weight and myofibril size in murine masseter muscle. Real-time RT-PCR analysis revealed significant downregulation of myostatin mRNA expression in both the Mstn-siRNA-treated and the combination treatment group. Furthermore, myogenin mRNA expression was upregulated in the combination treatment group, while MuRF-1 and Atrogin-1 mRNA expression was downregulated compared to administration of each compound alone. These findings suggest that double inhibition of myostatin is a potentially useful treatment strategy to increase muscle mass and fiber size and could be a useful treatment of patients with various muscle atrophies, including muscular dystrophy. (Tokushima University Institutional Repository) ● Metadata: 114288 (Link to Publication Site) ● Publication site (DOI): 10.3177/jnsv.63.244 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28978871 ● Search Scopus @ Elsevier (PMID): 28978871 ● Search Scopus @ Elsevier (DOI): 10.3177/jnsv.63.244 (Tokushima University Institutional Repository: 114288, DOI: 10.3177/jnsv.63.244, PubMed: 28978871)
40.	Mayumi Takeya, Yuushi Okumura and Takeshi Nikawa : Modulation of cutaneous extracellular collagen contraction by phosphorylation status of p130Cas., The Journal of Physiological Sciences, Vol.67, No.5, 613-622, 2016. (Summary) Skin can respond to various types of internal and/or external mechanostimuli, such as excessive tension caused by body growth or decompression due to weight loss, which significantly affect skin morphology. Mechanosensors, including p130Cas, are reported to play a role in deformation and subsequent recovery of various tissues including skeletal muscles and blood vessels. However, the role of mechanotransduction via p130Cas in the regulation of skin size remains unclear. In this report, p130Cas activation was manipulated using a fibroblast-embedded collagen gel model or mouse skin contraction model. Inhibition or activation of Src family kinase-mediated phosphorylation of p130Cas significantly depressed and accelerated collagen gel contraction, respectively. The results also demonstrated age-dependent depression of cutaneous p130Cas activation in vivo. Inhibition of p130Cas signaling in our mouse model significantly suppressed recovery from cutaneous deformation. Taken together, our study highlighted the important role of p130Cas in cutaneous mechanotransduction for skin homeostasis. (Link to Publication Site) ● Publication site (DOI): 10.1007/s12576-016-0493-9 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27718170 ● Search Scopus @ Elsevier (PMID): 27718170 ● Search Scopus @ Elsevier (DOI): 10.1007/s12576-016-0493-9 (DOI: 10.1007/s12576-016-0493-9, PubMed: 27718170)
41.	Rie Mukai, Hitomi Horikawa, Pei-Yi Lin, Nao Tsukumo, Takeshi Nikawa, Tomoyuki Kawamura, Hisao Nemoto and Junji Terao : 8-Prenylnaringenin promotes recovery from immobilization-induced disuse muscle atrophy through activation of the Akt phosphorylation pathway in mice., American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, Vol.311, No.6, R1022-R1031, 2016. (Summary) 8-Prenylnaringenin (8-PN) is a prenylflavonoid that originates from hop extracts and is thought to help prevent disuse muscle atrophy. We hypothesized that 8-PN affects muscle plasticity by promoting muscle recovery under disuse muscle atrophy. To test the promoting effect of 8-PN on muscle recovery, we administered an 8-PN mixed diet to mice that had been immobilized with a cast to one leg for 14 days. Intake of the 8-PN mixed diet accelerated recovery from muscle atrophy, and prevented reductions in Akt phosphorylation. Studies on cell cultures of mouse myotubes in vitro demonstrated that 8-PN activated the PI3K/Akt/P70S6K1 pathway at physiological concentrations. A cell-culture study using an inhibitor of estrogen receptors and an in vivo experiment with ovariectomized mice suggested that the estrogenic activity of 8-PN contributed to recovery from disuse muscle atrophy through activation of an Akt phosphorylation pathway. These data strongly suggest that 8-PN is a naturally occurring compound that could be used as a nutritional supplement to aid recovery from disuse muscle atrophy. (Keyword) Animals / Cell Line / Enzyme Activation / Flavanones / Hindlimb Suspension / Male / Mice / Mice, Inbred C57BL / Muscle Proteins / Muscle, Skeletal / Muscular Atrophy / Oncogene Protein v-akt / phosphorylation / Phytoestrogens / Protein Biosynthesis / Recovery of Function / signal transduction / Treatment Outcome (Tokushima University Institutional Repository) ● Metadata: 112458 (Link to Publication Site) ● Publication site (DOI): 10.1152/ajpregu.00521.2015 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27629889 ● Search Scopus @ Elsevier (PMID): 27629889 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpregu.00521.2015 (Tokushima University Institutional Repository: 112458, DOI: 10.1152/ajpregu.00521.2015, PubMed: 27629889)
42.	Katsuya Hirasaka, EM Mills, Haruna Marie, Bando Aki, Ikeda Chika, Tomoki Abe, Kohno Shohei, SM Nowinski, CU Lago, K Akagi, H Tochio, Ohno Ayako, Teshima-Kondo Shigetada, Yuushi Okumura and Takeshi Nikawa : UCP3 is associated with Hax-1 in mitochondria in the presence of calcium ion, Biochemical and Biophysical Research Communications, Vol.472, No.1, 108-113, 2016. (Summary) Uncoupling protein 3 (UCP3) is known to regulate energy dissipation, proton leakage, fatty acid oxidation, and oxidative stress. To identify the putative protein regulators of UCP3, we performed yeast two-hybrid screens. Here we report that UCP3 interacted with HS-1 associated protein X-1 (Hax-1), an anti-apoptotic protein that was localized in the mitochondria, and is involved in cellular responses to Ca(2+). The hydrophilic sequences within loop 2, and the matrix-localized hydrophilic domain of mouse UCP3, were necessary for binding to Hax-1 at the C-terminal domain, adjacent to the mitochondrial inner membrane. Interestingly, interaction of these proteins occurred in a calcium-dependent manner. Moreover, the NMR spectrum of the C-terminal domain of Hax-1 was dramatically changed by removal of Ca(2+), suggesting that the C-terminal domain of Hax-1 underwent a Ca(2+)-induced conformational change. In the Ca(2+)-free state, the C-terminal Hax-1 tended to unfold, suggesting that Ca(2+) binding may induce protein folding of the Hax-1 C-terminus. These results suggested that the UCP3-Hax-1 complex may regulate mitochondrial functional changes caused by mitochondrial Ca(2+). (Keyword) Animals / Calcium / HEK293 Cells / Humans / Ion Channels / Mice / Mitochondria / Mitochondrial Membranes / Mitochondrial Proteins / Models, Molecular / Nuclear Magnetic Resonance, Biomolecular / Protein Conformation / Protein Interaction Domains and Motifs / Proteins / Recombinant Fusion Proteins / Two-Hybrid System Techniques (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2016.02.075 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26915802 ● Summary page in Scopus @ Elsevier: 2-s2.0-84975678644 (DOI: 10.1016/j.bbrc.2016.02.075, PubMed: 26915802, Elsevier: Scopus)
43.	Ayako Ohno, Arisa Ochi, Nobuo Maita, Tatsuya Ueji, Aki Bando, Reiko Nakao, Katsuya Hirasaka, Tomoki Abe, Shigetada Teshima-Kondo, Hisao Nemoto, Yuushi Okumura, Akira Higashibata, Sachiko Yano, Hidehito Tochio and Takeshi Nikawa : Structural analysis of the TKB domain of ubiquitin ligase Cbl-b complexed with its small inhibitory peptide, Cblin., Archives of Biochemistry and Biophysics, Vol.594, 1-7, 2016. (Summary) Cbl-b is a RING-type ubiquitin ligase. Previously, we showed that Cbl-b-mediated ubiquitination and proteosomal degradation of IRS-1 contribute to muscle atrophy caused by unloading stress. The phospho-pentapeptide DGpYMP (Cblin) mimics Tyr612-phosphorylated IRS-1 and inhibits the Cbl-b-mediated ubiquitination and degradation of IRS-1 in vitro and in vivo. In this study, we confirmed the direct interaction between Cblin and the TKB domain of Cbl-b using NMR. Moreover, we showed that the shortened tripeptide GpYM also binds to the TKB domain. To elucidate the inhibitory mechanism of Cblin, we solved the crystal structure of the TKB-Cblin complex at a resolution of 2.5 Å. The pY in Cblin inserts into a positively charged pocket in the TKB domain via hydrogen-bond networks and hydrophobic interactions. Within this complex, the Cblin structure closely resembles the TKB-bound form of another substrate-derived phosphopeptide, Zap-70-derived phosphopeptide. These peptides lack the conserved intrapeptidyl hydrogen bond between pY and a conserved residue involved in TKB-domain binding. Instead of the conserved interaction, these peptides specifically interact with the TKB domain. Based on this binding mode of Cblin to the TKB domain, we can design drugs against unloading-mediated muscle atrophy. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.abb.2016.02.014 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26874193 ● Search Scopus @ Elsevier (PMID): 26874193 ● Search Scopus @ Elsevier (DOI): 10.1016/j.abb.2016.02.014 (DOI: 10.1016/j.abb.2016.02.014, PubMed: 26874193)
44.	Rie Mukai, Naoko Matsui, Yutaka Fujikura, Norifumi Matsumoto, De-Xing Hou, Noriyuki Kanzaki, Hiroshi Shibata, Manabu Horikawa, Keiko Iwasa, Katsuya Hirasaka, Takeshi Nikawa and Junji Terao : Preventive effect of dietary quercetin on disuse muscle atrophy by targeting mitochondria in denervated mice., The Journal of Nutritional Biochemistry, Vol.31, 67-76, 2016. (Summary) Quercetin is a major dietary flavonoid in fruits and vegetables. We aimed to clarify the preventive effect of dietary quercetin on disuse muscle atrophy and the underlying mechanisms. We established a mouse denervation model by cutting the sciatic nerve in the right leg (SNX surgery) to lack of mobilization in hind-limb. Preintake of a quercetin-mixed diet for 14days before SNX surgery prevented loss of muscle mass and atrophy of muscle fibers in the gastrocnemius muscle (GM). Phosphorylation of Akt, a key phosphorylation pathway of suppression of protein degradation, was activated in the quercetin-mixed diet group with and without SNX surgery. Intake of a quercetin-mixed diet suppressed the generation of hydrogen peroxide originating from mitochondria and elevated mitochondrial peroxisome proliferator-activated receptor- coactivator 1 mRNA expression as well as NADH dehydrogenase 4 expression in the GM with SNX surgery. Quercetin and its conjugated metabolites reduced hydrogen peroxide production in the mitochondrial fraction obtained from atrophied muscle. In C2C12 myotubes, quercetin reached the mitochondrial fraction. These findings suggest that dietary quercetin can prevent disuse muscle atrophy by targeting mitochondria in skeletal muscle tissue through protecting mitochondria from decreased biogenesis and reducing mitochondrial hydrogen peroxide release, which can be related to decreased hydrogen peroxide production and/or improvements on antioxidant capacity of mitochondria. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jnutbio.2016.02.001 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27133425 ● Search Scopus @ Elsevier (PMID): 27133425 ● Search Scopus @ Elsevier (DOI): 10.1016/j.jnutbio.2016.02.001 (DOI: 10.1016/j.jnutbio.2016.02.001, PubMed: 27133425)
45.	Katsuya Hirasaka, Shinobu Saito, Saki Yamaguchi, Riho Miyazaki, Yao Wang, Marie Haruna, Shigeto Taniyama, Atsushi Higashitani, Junji Terao, Takeshi Nikawa and Katsuyasu Tachibana : Dietary Supplementation with Isoflavones Prevents Muscle Wasting in Tumor-Bearing Mice., Journal of Nutritional Science and Vitaminology, Vol.62, No.3, 178-184, 2016. (Summary) Proinflammatory cytokines contribute to the progression of muscle wasting caused by ubiquitin-proteasome-dependent proteolysis. We have previously demonstrated that isoflavones, such as genistein and daidzein, prevent TNF--induced muscle atrophy in C2C12 myotubes. In this study, we examined the effect of dietary flavonoids on the wasting of muscle. Mice were divided into the following four groups: vehicle-injected (control) mice fed the normal diet (CN); tumor-bearing mice fed the normal diet (TN); control mice fed the isoflavone diet (CI); and tumor-bearing mice fed the isoflavone diet (TI). There were no significant differences in the intake of food or body weight gain among these four groups. The wet weight and myofiber size of gastrocnemius muscle in TN significantly decreased, compared with those in CN. Interestingly, the wet weight and myofiber size of gastrocnemius muscle in TI were nearly the same as those in CN and CI, although isoflavone supplementation did not affect the increased tumor mass or concentrations of proinflammatory cytokines, such as TNF- and IL-6, in the blood. Moreover, increased expression of muscle-specific ubiquitin ligase genes encoding MAFbx/Atrogin-1 and MuRF1 in the skeletal muscle of TN was significantly inhibited by the supplementation of isoflavones. In parallel with the expression of muscle-specific ubiquitin ligases, dietary isoflavones significantly suppressed phosphorylation of ERK in tumor-bearing mice. These results suggest that dietary isoflavones improve muscle wasting in tumor-bearing mice via the ERK signaling pathway mediated-suppression of ubiquitin ligases in muscle cells. (Keyword) Animals / Dietary Supplements / Extracellular Signal-Regulated MAP Kinases / Gene Expression / Interleukin-6 / Isoflavones / MAP Kinase Signaling System / Male / Mice / Mice, Inbred C57BL / Muscle, Skeletal / Muscular Atrophy / Neoplasms / Organ Size / Phosphorylation / Tumor Necrosis Factor-alpha / Ubiquitin-Protein Ligases / Wasting Syndrome (Link to Publication Site) ● Publication site (DOI): 10.3177/jnsv.62.178 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27465724 ● Search Scopus @ Elsevier (PMID): 27465724 ● Search Scopus @ Elsevier (DOI): 10.3177/jnsv.62.178 (DOI: 10.3177/jnsv.62.178, PubMed: 27465724)
46.	Tomoki Abe, Katsuya Hirasaka, Kohno Shohei, Tomida Chisato, Haruna Marie, Uchida Takayuki, Ohno Ayako, Oarada Motoko, Teshima-Kondo Shigetada, Yuushi Okumura, Choi Inho, Aoyama Toshiaki, Junji Terao and Takeshi Nikawa : Capric Acid Up-Regulates UCP3 Expression without PDK4 Induction in Mouse C2C12 Myotubes, Journal of Nutritional Science and Vitaminology, Vol.62, No.1, 32-39, 2016. (Summary) Uncoupling protein 3 (UCP3) and pyruvate dehydrogenase kinase 4 (PDK4) in skeletal muscle are key regulators of the glucose and lipid metabolic processes that are involved in insulin resistance. Medium-chain fatty acids (MCFAs) have anti-obesogenic effects in rodents and humans, while long-chain fatty acids (LCFAs) cause increases in body weight and insulin resistance. To clarify the beneficial effects of MCFAs, we examined UCP3 and PDK4 expression in skeletal muscles of mice fed a MCFA- or LCFA-enriched high-fat diet (HFD). Five-week feeding of the LCFA-enriched HFD caused high body weight gain and induced glucose intolerance in mice, compared with those in mice fed the MCFA-enriched HFD. However, the amounts of UCP3 and PDK4 transcripts in the skeletal muscle of mice fed the MCFA- or LCFA-enriched HFD were similar. To further elucidate the specific effects of MCFAs, such as capric acid (C10:0), on lipid metabolism in skeletal muscles, we examined the effects of various FAs on expression of UCP3 and PDK4, in mouse C2C12 myocytes. Although palmitic acid (C16:0) and lauric acid (C12:0) significantly induced expression of both UCP3 and PDK4, capric acid (C10:0) upregulated only UCP3 expression via activation of peroxisome proliferator-activated receptor-δ. Furthermore, palmitic acid (C16:0) disturbed the insulin-induced phosphorylation of Akt, while MCFAs, including lauric (C12:0), capric (C10:0), and caprylic acid (C12:0), did not. These results suggest that capric acid (C10:0) increases the capacity for fatty acid oxidation without inhibiting glycolysis in skeletal muscle. (Keyword) medium-chain fatty acids / PDK4 / PPARdelta / skeletal muscle / UCP3 (Link to Publication Site) ● Publication site (DOI): 10.3177/jnsv.62.32 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27117849 ● Summary page in Scopus @ Elsevier: 2-s2.0-84974539592 (DOI: 10.3177/jnsv.62.32, PubMed: 27117849, Elsevier: Scopus)
47.	M Sara Nowinski, Ashley Solmonson, E Joyce Rundhaug, Okkyung Rho, Jiyoon Cho, U Cory Lago, L Christopher Riley, Sunhee Lee, Shohei Kohno, K Christine Dao, Takeshi Nikawa, B Shawn Bratton, W Casey Wright, M Susan Fischer, John DiGiovanni and M Edward Mills : Mitochondrial uncoupling links lipid catabolism to Akt inhibition and resistance to tumorigenesis., Nature Communications, Vol.6, 2015. (Summary) To support growth, tumour cells reprogramme their metabolism to simultaneously upregulate macromolecular biosynthesis while maintaining energy production. Uncoupling proteins (UCPs) oppose this phenotype by inducing futile mitochondrial respiration that is uncoupled from ATP synthesis, resulting in nutrient wasting. Here using a UCP3 transgene targeted to the basal epidermis, we show that forced mitochondrial uncoupling inhibits skin carcinogenesis by blocking Akt activation. Similarly, Akt activation is markedly inhibited in UCP3 overexpressing primary human keratinocytes. Mechanistic studies reveal that uncoupling increases fatty acid oxidation and membrane phospholipid catabolism, and impairs recruitment of Akt to the plasma membrane. Overexpression of Akt overcomes metabolic regulation by UCP3, rescuing carcinogenesis. These findings demonstrate that mitochondrial uncoupling is an effective strategy to limit proliferation and tumorigenesis through inhibition of Akt, and illuminate a novel mechanism of crosstalk between mitochondrial metabolism and growth signalling. (Keyword) Animals / Carcinogenesis / Carcinogens / Cell Proliferation / Flow Cytometry / Gene Ontology / Humans / Immunoblotting / Ion Channels / Keratinocytes / Lipid Metabolism / Metabolome / Metabolomics / Mice / Mice, Transgenic / Mitochondria / Mitochondrial Proteins / Neoplasms, Experimental / Proto-Oncogene Proteins c-akt / Reactive Oxygen Species / Skin Neoplasms / Tetradecanoylphorbol Acetate (Tokushima University Institutional Repository) ● Metadata: 115642 (Link to Publication Site) ● Publication site (DOI): 10.1038/ncomms9137 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26310111 ● Search Scopus @ Elsevier (PMID): 26310111 ● Search Scopus @ Elsevier (DOI): 10.1038/ncomms9137 (Tokushima University Institutional Repository: 115642, DOI: 10.1038/ncomms9137, PubMed: 26310111)
48.	Chieko Shiota, Tomoki Abe, Nobuhiko Kawai, Ayako Ohno, Shigetada Teshima-Kondo, Hiroyo Mori, Junji Terao, Eiji Tanaka and Takeshi Nikawa : Flavones Inhibit LPS-Induced Atrogin-1/MAFbx Expression in Mouse C2C12 Skeletal Myotubes., Journal of Nutritional Science and Vitaminology, Vol.61, No.2, 188-194, 2015. (Summary) Muscle atrophy is a complex process that occurs as a consequence of various stress events. Muscle atrophy-associated genes (atrogenes) such as atrogin-1/MAFbx and MuRF-1 are induced early in the atrophy process, and the increase in their expression precedes the loss of muscle weight. Although antioxidative nutrients suppress atrogene expression in skeletal muscle cells, the inhibitory effects of flavonoids on inflammation-induced atrogin-1/MAFbx expression have not been clarified. Here, we investigated the inhibitory effects of flavonoids on lipopolysaccharide (LPS)-induced atrogin-1/MAFbx expression. We examined whether nine flavonoids belonging to six flavonoid categories inhibited atrogin-1/MAFbx expression in mouse C2C12 myotubes. Two major flavones, apigenin and luteolin, displayed potent inhibitory effects on atrogin-1/MAFbx expression. The pretreatment with apigenin and luteolin significantly prevented the decrease in C2C12 myotube diameter caused by LPS stimulation. Importantly, the pretreatment of LPS-stimulated myoblasts with these flavones significantly inhibited LPS-induced JNK phosphorylation in C2C12 myotubes, resulting in the significant suppression of atrogin-1/MAFbx promoter activity. These results suggest that apigenin and luteolin, prevent LPS-mediated atrogin-1/MAFbx expression through the inhibition of the JNK signaling pathway in C2C12 myotubes. Thus, these flavones, apigenin and luteolin, may be promising agents to prevent LPS-induced muscle atrophy. (Tokushima University Institutional Repository) ● Metadata: 109398 (Link to Publication Site) ● Publication site (DOI): 10.3177/jnsv.61.188 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26052151 ● Summary page in Scopus @ Elsevier: 2-s2.0-84930695782 (Tokushima University Institutional Repository: 109398, DOI: 10.3177/jnsv.61.188, PubMed: 26052151, Elsevier: Scopus)
49.	Hikaru Nagano, Naoko Yamagishi, Chisato Tomida, Chiaki Yano, Kana Aibara, Shohei Kohno, Tomoki Abe, Ayako Maita, Katsuya Hirasaka, Yuushi Okumura, M Edward Mills, Takeshi Nikawa and Shigetada Kondo : A novel myogenic function residing in the 5' non-coding region of Insulin receptor substrate-1 (Irs-1) transcript., BMC Cell Biology, Vol.16, 8, 2015. (Summary) Our findings suggest that the FL-Irs-1 transcript regulates myogenic differentiation as a regulatory RNA in myoblasts. (Keyword) 5' Untranslated Regions / Animals / Base Sequence / Cell Differentiation / Cell Line / Insulin Receptor Substrate Proteins / Mice / Muscle, Skeletal / Myoblasts / RNA Interference / RNA, Messenger / RNA, Small Interfering / Retinoblastoma Protein / Sequence Alignment (Tokushima University Institutional Repository) ● Metadata: 114747 (Link to Publication Site) ● Publication site (DOI): 10.1186/s12860-015-0054-8 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25887310 ● Summary page in Scopus @ Elsevier: 2-s2.0-84925295420 (Tokushima University Institutional Repository: 114747, DOI: 10.1186/s12860-015-0054-8, PubMed: 25887310, Elsevier: Scopus)
50.	Ichiro Tonogai, Mitsuhiko Takahashi, Kiminori Yukata, Ryosuke Sato, Takeshi Nikawa, Natsuo Yasui and Koichi Sairyo : Osteoactivin attenuates skeletal muscle fibrosis after distraction osteogenesis by promoting extracellular matrix degradation/remodeling., Journal of Pediatric Orthopaedics. Part B, Vol.24, No.2, 162-169, 2015. (Summary) The aim of this study was to determine whether osteoactivin attenuated skeletal muscle fibrosis caused by distraction osteogenesis. Tibial osteotomies were performed on wild-type and osteoactivin-transgenic (OA-Tg) mice, and tibiae were distracted for 2 weeks. Ankle plantar flexion torque and the gastrocnemius muscles were analyzed. The amount and area of collagenous tissue and the passive torque were reduced in the OA-Tg group at 8 weeks after osteotomy. Transcript levels of matrix metalloprotease (mmp)-3 and MMP-9 were upregulated, and MMP-3 and MMP-9 proteins were increased in the OA-Tg group. Osteoactivin-mediated increase in MMPs may attenuate skeletal muscle fibrosis. (Tokushima University Institutional Repository) ● Metadata: 109371 (Link to Publication Site) ● Publication site (DOI): 10.1097/BPB.0000000000000117 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25405936 ● Summary page in Scopus @ Elsevier: 2-s2.0-84922398143 (Tokushima University Institutional Repository: 109371, DOI: 10.1097/BPB.0000000000000117, PubMed: 25405936, Elsevier: Scopus)
51.	Arisa Ochi, Tomoki Abe, Reiko Nakao, Yoriko Yamamoto, Kanako Kitahata, Marina Takagi, Katsuya Hirasaka, Ayako Ohno, Shigetada Teshima-Kondo, Gwag Taesik, Inho Choi, Tomoyuki Kawamura, Hisao Nemoto, Rie Mukai, Junji Terao and Takeshi Nikawa : N-myristoylated ubiquitin ligase Cbl-b inhibitor prevents on glucocorticoid-induced atrophy in mouse skeletal muscle., Archives of Biochemistry and Biophysics, Vol.570, 23-31, 2015. (Summary) A DGpYMP peptide mimetic of tyrosine(608)-phosphorylated insulin receptor substrate-1 (IRS-1), named Cblin, was previously shown to significantly inhibit Cbl-b-mediated IRS-1 ubiquitination. In the present study, we developed N-myristoylated Cblin and investigated whether it was effective in preventing glucocorticoid-induced muscle atrophy. Using HEK293 cells overexpressing Cbl-b, IRS-1 and ubiquitin, we showed that the 50% inhibitory concentrations of Cbl-b-mediated IRS-1 ubiquitination by N-myristoylated Cblin and Cblin were 30 and 120M, respectively. Regarding the DEX-induced atrophy of C2C12 myotubes, N-myristoylated Cblin was more effective than Cblin for inhibiting the DEX-induced decreases in C2C12 myotube diameter and IRS-1 degradation. The inhibitory efficacy of N-myristoylated Cblin on IRS-1 ubiquitination in C2C12 myotubes was approximately fourfold larger than that of Cblin. Furthermore, N-myristoylation increased the incorporation of Cblin into HEK293 cells approximately 10-folds. Finally, we demonstrated that N-myristoylated Cblin prevented the wet weight loss, IRS-1 degradation, and MAFbx/atrogin-1 and MuRF-1 expression in gastrocnemius muscle of DEX-treated mice approximately fourfold more effectively than Cblin. Taken together, these results suggest that N-myristoylated Cblin prevents DEX-induced skeletal muscle atrophy in vitro and in vivo, and that N-myristoylated Cblin more effectively prevents muscle atrophy than unmodified Cblin. (Tokushima University Institutional Repository) ● Metadata: 109380 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.abb.2015.02.006 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25689493 ● Summary page in Scopus @ Elsevier: 2-s2.0-84924084788 (Tokushima University Institutional Repository: 109380, DOI: 10.1016/j.abb.2015.02.006, PubMed: 25689493, Elsevier: Scopus)
52.	Nobuhiko Kawai, Katsuya Hirasaka, Tasuku Maeda, Marie Haruna, Chieko Shiota, Arisa Ochi, Tomoki Abe, Shohei Kohno, Ayako Ohno, Sigetada Teshima-Kondo, Hiroyo Mori, Eiji Tanaka and Takeshi Nikawa : Prevention of skeletal muscle atrophy in vitro using anti-ubiquitination oligopeptide carried by atelocollagen., Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol.1853, No.5, 873-880, 2015. (Summary) Skeletal muscle atrophy occurs when the rate of protein degradation exceeds that of protein synthesis in various catabolic conditions, such as fasting, disuse, aging, and chronic diseases. Insulin-like growth factor-1 (IGF-1) signaling stimulates muscle growth and suppresses muscle protein breakdown. In atrophied muscles, ubiquitin ligase, Cbl-b, increases and stimulates the ubiquitination and degradation of IRS-1, an intermediate in IGF-1 signaling pathway, resulting in IGF-1 resistance. In this study, we evaluated the efficacy of atelocollagen (ATCOL)-transported anti-ubiquitination oligopeptide (Cblin: Cbl-b inhibitor) (consisting of tyrosine phosphorylation domain of IRS-1) in starved C2C12 myotubes. The amount of IRS-1 protein was lower in starved versus unstarved myotubes. The Cblin-ATCOL complex inhibited IRS-1 degradation in a concentration-dependent manner. Myotubes incubated with Cblin-ATCOL complex showed significant resistance to starvation-induced atrophy (p<0.01). Furthermore, the Cblin-ATCOL complex significantly inhibited any decrease in Akt phosphorylation (p<0.01) and localization of FOXO3a to the nucleus in starved myotubes. These results suggest that Cblin prevented starvation-induced C2C12 myotube atrophy by maintaining the IGF-1/Akt/FOXO signaling. Therefore, attachment of anti-ubiquitination oligopeptide, Cblin, to ATCOL enhances its delivery to myotubes and could be a potentially effective strategy in the treatment of atrophic myopathies. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbamcr.2015.01.024 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25667084 ● Summary page in Scopus @ Elsevier: 2-s2.0-84923091632 (DOI: 10.1016/j.bbamcr.2015.01.024, PubMed: 25667084, Elsevier: Scopus)
53.	Rie Hashimoto, Atsuko Sakai, Masumi Murayama, Arisa Ochi, Tomoki Abe, Katsuya Hirasaka, Ayako Ohno, Shigetada Teshima-Kondo, Hiroaki Yanagawa, Natsuo Yasui, Mikiko Inatsugi, Daisuke Doi, Masanori Takeda, Rie Mukai, Junji Terao and Takeshi Nikawa : Effects of dietary soy protein on skeletal muscle volume and strength in humans with various physical activities, The Journal of Medical Investigation : JMI, Vol.62, No.3, 177-183, 2015. (Summary) Background: In recent years, the number of bedridden people is rapidly increasing due to aging or lack of exercise in Japan. This problem is becoming more serious, since there is no countermeasure against it. In the present study, we designed to investigate whether dietary proteins, especially soy, had beneficial effects on skeletal muscle in 59 volunteers with various physical activities. Methods: We subjected 59 volunteers with various physical activities to meal intervention examination. Persons with low and high physical activities were divided into two dietary groups, the casein diet group and the soy diet group. They ate daily meals supplemented with 7.8 g of powdered casein or soy protein isolate every day for 30 days. Bedridden patients in hospitals were further divided into three dietary groups: the no supplementation diet group, the casein diet group and the soy diet group. They were also subjected to a blood test, a urinalysis, magnetic resonance imaging analysis and muscle strength test of the knee before and after the meal intervention study. Results: Thirty-day soy protein supplementation significantly increased skeletal muscle volume in participants with low physical activity, compared with 30-day casein protein supplementation. Both casein and soy protein supplementation increased the volume of quadriceps femoris muscle in bedridden patients. Consistently, soy protein significantly increased their extension power of the knee, compared with casein protein. Although casein protein increased skeletal muscle volume more than soy protein in bedridden patients, their muscle strength changes by soy protein supplementation were bigger than those by casein protein supplementation. Conclusions: The supplementation of soy protein would be one of the effective foods which prevent the skeletal muscle atrophy caused by immobilization or unloading. J. Med. Invest. 62: 177-183, August, 2015 (Tokushima University Institutional Repository) ● Metadata: 109381 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.62.177 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26399344 ● CiNii @ National Institute of Informatics (CRID): 1390282679220909952 ● Summary page in Scopus @ Elsevier: 2-s2.0-84942054092 (Tokushima University Institutional Repository: 109381, DOI: 10.2152/jmi.62.177, PubMed: 26399344, CiNii: 1390282679220909952, Elsevier: Scopus)
54.	Chisato Tomida, Kana Aibara, Naoko Yamagishi, Chiaki Yano, Hikaru Nagano, Tomoki Abe, Ayako Ohno, Katsuya Hirasaka, Takeshi Nikawa and Shigetada Teshima-Kondo : The malignant progression effects of regorafenib in human colon cancer cells., The Journal of Medical Investigation : JMI, Vol.62, No.3-4, 195-198, 2015. (Summary) A number of anti-angiogenic drugs targeting vascular endothelial growth factor receptors (VEGF-R) have developed and enabled significant advances in cancer therapy including colorectal cancer. However, acquired resistance to the drugs occurs, leading to disease progression, such as invasion and metastasis. How tumors become the resistance and promote their malignancy remains fully uncertain. One of possible mechanisms for the resistance and the progression may be the direct effect of VEGF-R inhibitors on tumor cells expressing VEGF-R. We investigated here the direct effect of a VEGF-R-targeting agent, regorafenib, which is the first small molecule inhibitor of VEGF-Rs for the treatment of patients with colorectal cancer, on phenotype changes in colon cancer HCT116 cells. Treatment of cells with regorafenib for only 2 days activated cell migration and invasion, while vehicle-treated control cells showed less activity. Intriguingly, chronic exposure to regorafenib for 90 days dramatically increased migration and invasion activities and induced a resistance to hypoxia-induced apoptosis. These results suggest that loss of VEGF signaling in cancer cells may induce the acquired resistance to VEGF/VEGF-R targeting therapy by gaining two major malignant phenotypes, apoptosis resistance and activation of migration/invasion. (Tokushima University Institutional Repository) ● Metadata: 111278 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.62.195 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26399347 ● Search Scopus @ Elsevier (PMID): 26399347 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.62.195 (Tokushima University Institutional Repository: 111278, DOI: 10.2152/jmi.62.195, PubMed: 26399347)
55.	Chisato Tomida, Naoko Yamagishi, Kana Aibara, Chiaki Yano, Takayuki Uchida, Tomoki Abe, Ayako Ohno, Katsuya Hirasaka, Takeshi Nikawa and Shigetada Teshima-Kondo : Chronic exposure of VEGF inhibitors promotes the malignant phenotype of colorectal cancer cells., The Journal of Medical Investigation : JMI, Vol.62, No.1-2, 75-79, 2015. (Summary) VEGF-targeting anti-angiogenic drugs have enabled significant advances in cancer therapy. However, acquired resistance to VEGF-targeting drugs occurs, leading to disease progression. How tumors become the resistance remains fully uncertain. One of possible mechanisms for the resistance may be the direct effect of VEGF inhibitors on tumor cells expressing VEGF receptors (VEGF-R). We investigated here the direct effect of chronic VEGF inhibition on phenotype changes in cancer cells. To chronically inhibit cancer cell-derived VEGF, human colon cancer HCT116 cells were chronically exposed (3 months) to anti-VEGF neutralizing monoclonal antibody (HCT/mAb cells, blockade of VEGF alone) or VEGF-R tyrosine kinase inhibitor foretinib (HCT/fore cells, blockade of all VEGF family). HCT/mAb cells redundantly increased VEGF family member (VEGF, PlGF, VEGF-B, VEGF-R1 and VEGF-R2) and induced a resistance to hypoxia-induced apoptosis. By contrast, HCT/fore cells did not show the redundant increase in VEGF family member, but significantly increased a VEGF-independent pro-angiogenic factor FGF-2. HCT/fore cells showed increased migration and invasion activities in addition to a resistance to hypoxia-induced apoptosis. The resistance to apoptosis was significantly suppressed by inhibition of hypoxia-inducible factor-1 in HCT/mAb cells, but not in HCT/fore cells. These findings suggest that chronic inhibition of VEGF/VEGF-R accelerates malignant phenotypes of colon cancer cells. J. Med. Invest. 62: 75-79, February, 2015. (Tokushima University Institutional Repository) ● Metadata: 111254 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.62.75 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25817288 ● Summary page in Scopus @ Elsevier: 2-s2.0-84925846264 (Tokushima University Institutional Repository: 111254, DOI: 10.2152/jmi.62.75, PubMed: 25817288, Elsevier: Scopus)
56.	Motoko Oarada, Azusa Takahashi-Nakaguchi, Tomoki Abe, Takeshi Nikawa, Takashi Miki and Tohru Gonoi : Refeeding with glucose rather than fructose elicits greater hepatic inflammatory gene expression in mice., Nutrition, Vol.31, No.5, 757-765, 2014. (Summary) Dietary glucose, rather than fructose, plays a critical role in refeeding-induced acute liver inflammatory gene expression and moderate hepatocyte destruction. Further studies are recommended regarding the role of these effects in liver inflammation and, consequently, liver dysfunction. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.nut.2014.11.014 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25837224 ● Search Scopus @ Elsevier (PMID): 25837224 ● Search Scopus @ Elsevier (DOI): 10.1016/j.nut.2014.11.014 (DOI: 10.1016/j.nut.2014.11.014, PubMed: 25837224)
57.	Hirokazu Shiheido, Takane Aoyama, Honami Takahashi, Kaori Hanaoka, Tomoki Abe, Emi Nishida, Chen Chen, Orie Koga, Masaki Hikida, Yoshio Shibagaki, Akimichi Morita, Takeshi Nikawa, Seisuke Hattori, Takeshi Watanabe and Jun Shimizu : Novel CD3-specific antibody induces immunosuppression via impaired phosphorylation of LAT and PLC1 following T-cell stimulation., European Journal of Immunology, Vol.44, No.6, 1770-1780, 2014. (Summary) The activation of T cells is known to be accompanied by the temporary downmodulation of the TCR/CD3 complex on the cell surface. Here, we established a novel monoclonal antibody, Dow2, that temporarily induces downmodulation of the TCR/CD3 complex in mouse CD4(+) T cells without activating T cells. Dow2 recognized the determinant on CD3; however, differences were observed in the binding mode between Dow2 and the agonistic anti-CD3 Ab, 145-2C11. An injection of Dow2 in vivo resulted in T-cell anergy, and prolonged the survival of cardiac allografts without a marked increase in cytokine release. The phosphorylated forms of the signaling proteins PLC-1 and LAT in Dow2-induced anergic T cells were markedly decreased upon stimulation. However, the levels of phosphorylated LAT and PLC1 in Dow2-induced anergic T cells could be rescued in the presence of the proteasome inhibitor MG-132. These results suggest that proteasome-mediated degradation is involved in hypophosphorylated LAT and PLC1 in Dow2-induced anergic T cells. The novel CD3-specific Ab, Dow2, may provide us with a unique tool for inducing immunosuppression. (Keyword) Adaptor Proteins, Signal Transducing / Animals / Antibodies, Monoclonal, Murine-Derived / Antigens, CD3 / Clonal Anergy / Male / Membrane Proteins / Mice / Mice, Inbred BALB C / Phospholipase C gamma / Phosphoproteins / Phosphorylation / Proteasome Endopeptidase Complex / Proteolysis / T-Lymphocytes (Link to Publication Site) ● Publication site (DOI): 10.1002/eji.201344146 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24595757 ● Search Scopus @ Elsevier (PMID): 24595757 ● Search Scopus @ Elsevier (DOI): 10.1002/eji.201344146 (DOI: 10.1002/eji.201344146, PubMed: 24595757)
58.	Taesik Gwag, Kyoungsook Park, Eunjung Kim, Chaeyeon Son, Junsoo Park, Takeshi Nikawa and Inho Choi : Inhibition of C2C12 myotube atrophy by a novel HSP70 inducer, celastrol, via activation of Akt1 and ERK1/2 pathways., Archives of Biochemistry and Biophysics, Vol.537, No.1, 21-30, 2013. (Summary) Celastrol (CEL) is known as a potent inducer of heat shock protein (HSP) in non-muscle cells and exhibits cytoprotective function and inhibitory effects on proteasome and glucocorticoid receptor activities. To investigate an anti-atrophic effect of CEL on skeletal muscle cells, C2C12 myotubes were treated with 150 M dexamethasone (DEX) for 24h and 1.5 M CEL was added for the last 6h during the 24h DEX treatment. Compared to the control, the myotube diameter was reduced by a factor of 0.30 by DEX, but CEL treatment almost abrogated the DEX-induced atrophy. CEL treatment also increased expression of HSP72 and phosphorylation of heat shock transcription factor 1 (p-HSF1) 11-fold and 3.4-fold, respectively, as well as accumulation of p-HSF1 in the nucleus. Furthermore, CEL treatment elevated activities of Akt1, p70/S6K and ERK1/2 2.0- to 4.4-fold whereas DEX had no effect on these signaling activities. Inhibition of Akt1 and ERK1/2 pathways by specific inhibitors confirmed CEL-induced anti-atrophic effect. Moreover, DEX-mediated downregulation of FoxO3 phosphorylation and upregulation of MuRF1 expression and proteasome activity were abrogated by CEL treatment. These results demonstrate a novel anti-atrophic function of CEL in muscle cells via both activation of protein anabolic signals and suppression of catabolic signaling activities. (Keyword) Animals / Apoptosis / Cell Line / DNA-Binding Proteins / Enzyme Activation / HSP70 Heat-Shock Proteins / MAP Kinase Signaling System / Mice / Muscle Fibers, Skeletal / Muscular Atrophy / Protein Kinase Inhibitors / Proto-Oncogene Proteins c-akt / Transcription Factors / Triterpenes (Link to Publication Site) ● Publication site (DOI): 10.1016/j.abb.2013.06.006 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23810294 ● Search Scopus @ Elsevier (PMID): 23810294 ● Search Scopus @ Elsevier (DOI): 10.1016/j.abb.2013.06.006 (DOI: 10.1016/j.abb.2013.06.006, PubMed: 23810294)
59.	Tomoki Abe, Shohei Kohno, Tomonari Yama, Arisa Ochi, Takuro Suto, Katsuya Hirasaka, Ayako Ohno, Shigetada Teshima-Kondo, Yuushi Okumura, Motoko Oarada, Inho Choi, Rie Mukai, Junji Terao and Takeshi Nikawa : Soy Glycinin Contains a Functional Inhibitory Sequence against Muscle-Atrophy-Associated Ubiquitin Ligase Cbl-b., International Journal of Endocrinology, Vol.2013, 907565, 2013. (Summary) Background. Unloading stress induces skeletal muscle atrophy. We have reported that Cbl-b ubiquitin ligase is a master regulator of unloading-associated muscle atrophy. The present study was designed to elucidate whether dietary soy glycinin protein prevents denervation-mediated muscle atrophy, based on the presence of inhibitory peptides against Cbl-b ubiquitin ligase in soy glycinin protein. Methods. Mice were fed either 20% casein diet, 20% soy protein isolate diet, 10% glycinin diet containing 10% casein, or 20% glycinin diet. One week later, the right sciatic nerve was cut. The wet weight, cross sectional area (CSA), IGF-1 signaling, and atrogene expression in hindlimb muscles were examined at 1, 3, 3.5, or 4 days after denervation. Results. 20% soy glycinin diet significantly prevented denervation-induced decreases in muscle wet weight and myofiber CSA. Furthermore, dietary soy protein inhibited denervation-induced ubiquitination and degradation of IRS-1 in tibialis anterior muscle. Dietary soy glycinin partially suppressed the denervation-mediated expression of atrogenes, such as MAFbx/atrogin-1 and MuRF-1, through the protection of IGF-1 signaling estimated by phosphorylation of Akt-1. Conclusions. Soy glycinin contains a functional inhibitory sequence against muscle-atrophy-associated ubiquitin ligase Cbl-b. Dietary soy glycinin protein significantly prevented muscle atrophy after denervation in mice. (Link to Publication Site) ● Publication site (DOI): 10.1155/2013/907565 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23762056 ● Search Scopus @ Elsevier (PMID): 23762056 ● Search Scopus @ Elsevier (DOI): 10.1155/2013/907565 (DOI: 10.1155/2013/907565, PubMed: 23762056)
60.	Naoko Yamagishi, Shigetada Kondo, Kiyoshi Masuda, Kensei Nishida, Yuki Kuwano, Duyen T Dang, Long H Dang, Takeshi Nikawa and Kazuhito Rokutan : Chronic inhibition of tumor cell-derived VEGF enhances the malignant phenotype of colorectal cancer cells, BMC Cancer, Vol.13, 229, 2013. (Summary) Vascular endothelial growth factor-a (VEGF)-targeted therapies have become an important treatment for a number of human malignancies. The VEGF inhibitors are actually effective in several types of cancers, however, the benefits are transiently, and the vast majority of patients who initially respond to the therapies will develop resistance. One of possible mechanisms for the acquired resistance may be the direct effect(s) of VEGF inhibitors on tumor cells expressing VEGF receptors (VEGFR). Thus, we investigated here the direct effect of chronic VEGF inhibition on phenotype changes in human colorectal cancer (CRC) cells. To chronically inhibit cancer cell-derived VEGF, human CRC cell lines (HCT116 and RKO) were chronically exposed (2 months) to an anti-VEGF monoclonal antibody (mAb) or were disrupted the Vegf gene (VEGF-KO). Effects of VEGF family members were blocked by treatment with a VEGF receptor tyrosine kinase inhibitor (VEGFR-TKI). Hypoxia-induced apoptosis under VEGF inhibited conditions was measured by TUNEL assay. Spheroid formation ability was assessed using a 3-D spheroid cell culture system. Chronic inhibition of secreted/extracellular VEGF by an anti-VEGF mAb redundantly increased VEGF family member (PlGF, VEGFR1 and VEGFR2), induced a resistance to hypoxia-induced apoptosis, and increased spheroid formation ability. This apoptotic resistance was partially abrogated by a VEGFR-TKI, which blocked the compensate pathway consisted of VEGF family members, or by knockdown of Vegf mRNA, which inhibited intracellular function(s) of all Vegf gene products. Interestingly, chronic and complete depletion of all Vegf gene products by Vegf gene knockout further augmented these phenotypes in the compensate pathway-independent manner. These accelerated phenotypes were significantly suppressed by knockdown of hypoxia-inducible factor-1α that was up-regulated in the VEGF-KO cell lines. Our findings suggest that chronic inhibition of tumor cell-derived VEGF accelerates tumor cell malignant phenotypes. (Keyword) analysis of variance / Antibodies, Monoclonal / apoptosis / Enzyme Inhibitors / Gene Knockdown Techniques / HCT116 Cells / Humans / Hypoxia-Inducible Factor 1 / Phenotype / Pregnancy Proteins / Spheroids, Cellular / Vascular Endothelial Growth Factor A / Vascular Endothelial Growth Factor Receptor-1 / Vascular Endothelial Growth Factor Receptor-2 (Tokushima University Institutional Repository) ● Metadata: 105896 (Link to Publication Site) ● Publication site (DOI): 10.1186/1471-2407-13-229 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23651517 ● Summary page in Scopus @ Elsevier: 2-s2.0-84877039223 (Tokushima University Institutional Repository: 105896, DOI: 10.1186/1471-2407-13-229, PubMed: 23651517, Elsevier: Scopus)
61.	Tomoki Abe, Katsuya Hirasaka, Sachiko Kagawa, Shohei Kohno, Arisa Ochi, Kenro Utsunomiya, Atsuko Sakai, Ayako Maita, Shigetada Teshima-Kondo, Yuushi Okumura, Motoko Oarada, Yoichi Maekawa, Junji Terao, Edward M. Mills and Takeshi Nikawa : Cbl-b is a critical regulator of macrophage activation associated with obesity-induced insulin resistance in mice., Diabetes, Vol.62, No.6, 1957-1969, 2013. (Summary) We previously reported the potential involvement of casitas B-cell lymphoma-b (Cbl-b) in aging-related murine insulin resistance. Because obesity also induces macrophage recruitment into adipose tissue, we elucidated here the role of Cbl-b in obesity-related insulin resistance. Cbl-b(+/+) and Cbl-b(-/-) mice were fed a high-fat diet (HFD) and then examined for obesity-related changes in insulin signaling. The HFD caused recruitment of macrophages into adipose tissue and increased inflammatory reaction in Cbl-b(-/-) compared with Cbl-b(+/+) mice. Peritoneal macrophages from Cbl-b(-/-) mice and Cbl-b-overexpressing RAW264.7 macrophages were used to examine the direct effect of saturated fatty acids (FAs) on macrophage activation. In macrophages, Cbl-b suppressed saturated FA-induced Toll-like receptor 4 (TLR4) signaling by ubiquitination and degradation of TLR4. The physiological role of Cbl-b in vivo was also examined by bone marrow transplantation and Eritoran, a TLR4 antagonist. Hematopoietic cell-specific depletion of the Cbl-b gene induced disturbed responses on insulin and glucose tolerance tests. Blockade of TLR4 signaling by Eritoran reduced fasting blood glucose and serum interleukin-6 levels in obese Cbl-b(-/-) mice. These results suggest that Cbl-b deficiency could exaggerate HFD-induced insulin resistance through saturated FA-mediated macrophage activation. Therefore, inhibition of TLR4 signaling is an attractive therapeutic strategy for treatment of obesity-related insulin resistance. (Keyword) Adaptor Proteins, Signal Transducing / Animals / Cell Line / Flow Cytometry / Humans / Immunoblotting / Immunoprecipitation / insulin resistance / Macrophage Activation / Mice / knockout mice / NF-kappa B / obesity / Proto-Oncogene Proteins c-cbl / Real-Time Polymerase Chain Reaction (Tokushima University Institutional Repository) ● Metadata: 106157 (Link to Publication Site) ● Publication site (DOI): 10.2337/db12-0677 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23349502 ● Summary page in Scopus @ Elsevier: 2-s2.0-84878253581 (Tokushima University Institutional Repository: 106157, DOI: 10.2337/db12-0677, PubMed: 23349502, Elsevier: Scopus)
62.	Motoko Oarada, Takashi Miki, Shohei Kohno, Kanae Sakai, Takeshi Nikawa, Mitsutoshi Yoneyama and Tohru Gonoi : Refeeding with a standard diet after a 48-h fast elicits an inflammatory response in the mouse liver., The Journal of Nutritional Biochemistry, Vol.24, No.7, 1314-1323, 2013. (Summary) Unhealthy eating behaviors increase the risk of metabolic diseases, but the underlying mechanisms are not fully elucidated. Because inflammation contributes to the pathogenesis of metabolic diseases, it is important to understand the effects of unhealthy eating on the inflammatory state. The objective of our present study was to address the effects of a fasting-refeeding regime, a model of irregular eating, on the hepatic inflammatory responses in mouse. The animals were fasted for 48 h and then refed either a standard or low-carbohydrate/high-fat diet. Inflammatory gene expression in the liver was then sequentially measured for the first 17 h after initiation of refeeding. To assess the roles of dietary carbohydrates and toll-like receptor 2 (TLR2) in the refeeding-induced inflammatory changes, gene expression levels in mice refed only carbohydrates (-corn starch and sucrose) at different doses and in TLR2-deficient mice refed a standard diet were also analyzed. Refeeding with a standard diet increased the liver expression of Tlr2, proinflammatory mediators (Cxcl10, Cxcl1, Cxcl2, Icam-1) and negative regulators of TLR-signaling (A20 and Atf3). These increases were attenuated in mice refed a low-carbohydrate/high-fat diet. Refeeding only -corn starch and sucrose also increased the expression of these inflammatory pathway genes depending on the doses. TLR2 deficiency significantly attenuated the refeeding-induced increase in the liver expression of Cxcl10, Cxcl1, Icam-1 and A20. These findings suggest that an irregular eating behavior can elicit a liver inflammatory response, which is at least partly mediated by TLR2, and that dietary carbohydrates play critical roles in this process. (Keyword) Animal Feed / Animals / Base Sequence / Blood Glucose / DNA Primers / Fasting / Fatty Acids, Nonesterified / Female / Inflammation / Insulin / Liver / Mice / Mice, Inbred BALB C / Mice, Knockout / Real-Time Polymerase Chain Reaction / Reverse Transcriptase Polymerase Chain Reaction / Toll-Like Receptor 2 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jnutbio.2012.10.006 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23333091 ● Search Scopus @ Elsevier (PMID): 23333091 ● Search Scopus @ Elsevier (DOI): 10.1016/j.jnutbio.2012.10.006 (DOI: 10.1016/j.jnutbio.2012.10.006, PubMed: 23333091)
63.	Katsuya Hirasaka, Tasuku Maeda, Chika Ikeda, Marie Haruna, Arisa Ochi, Rie Mukai, Motoko Oarada, Shigetada Kondo, Ayako Ohno, Yuushi Okumura, Junji Terao and Takeshi Nikawa : Isoflavones derived from soy beans prevent MuRF1-mediated muscle atrophy in C2C12 myotubes through SIRT1 activation., Journal of Nutritional Science and Vitaminology, Vol.59, No.4, 317-324, 2013. (Summary) Proinflammatory cytokines are factors that induce ubiquitin-proteasome-dependent proteolysis in skeletal muscle, causing muscle atrophy. Although isoflavones, as potent antioxidative nutrients, have been known to reduce muscle damage during the catabolic state, the non-antioxidant effects of isoflavones against muscle atrophy are not well known. Here we report on the inhibitory effects of isoflavones such as genistein and daidzein on muscle atrophy caused by tumor necrosis factor (TNF)- treatment. In C2C12 myotubes, TNF- treatment markedly elevated the expression of the muscle-specific ubiquitin ligase MuRF1, but not of atrogin-1, leading to myotube atrophy. We found that MuRF1 promoter activity was mediated by acetylation of p65, a subunit of NFB, a downstream target of the TNF- signaling pathway; increased MuRF1 promoter activity was abolished by SIRT1, which is associated with deacetylation of p65. Of interest, isoflavones induced expression of SIRT1 mRNA and phosphorylation of AMP kinase, which is well known to stimulate SIRT1 expression, although there was no direct effect on SIRT1 activation. Moreover, isoflavones significantly suppressed MuRF1 promoter activity and myotube atrophy induced by TNF- in C2C12 myotubes. These results suggest that isoflavones suppress myotube atrophy in skeletal muscle cells through activation of SIRT1 signaling. Thus, the efficacy of isoflavones could provide a novel therapeutic approach against inflammation-related muscle atrophy. (Keyword) Acetylation / Adenylate Kinase / Animals / Antioxidants / Cell Line / Inflammation / Isoflavones / Mice / Muscle Fibers, Skeletal / Muscle Proteins / Muscular Atrophy / NF-kappa B / Phosphorylation / Phytotherapy / Plant Extracts / Promoter Regions, Genetic / RNA, Messenger / SKP Cullin F-Box Protein Ligases / Signal Transduction / Sirtuin 1 / Soybeans / Transcription Factor RelA / Tumor Necrosis Factor-alpha / Ubiquitin-Protein Ligases (Link to Publication Site) ● Publication site (DOI): 10.3177/jnsv.59.317 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24064732 ● CiNii @ National Institute of Informatics (CRID): 1390001206324728576 ● Summary page in Scopus @ Elsevier: 2-s2.0-84884576219 (DOI: 10.3177/jnsv.59.317, PubMed: 24064732, CiNii: 1390001206324728576, Elsevier: Scopus)
64.	Kenro Utsunomiya, Kanako Owaki, Yuushi Okumura, Momoko Yano, Takahiro Oto, Eri Suzuki, Seiko Tamura, Tomoki Abe, Shohei Kohno, Ayako Maita, Katsuya Hirasaka, Shigetada Kondo and Takeshi Nikawa : An intracellular fragment of osteoactivin formed by ectodomain shedding translocated to the nucleoplasm and bound to RNA binding proteins., Bioscience, Biotechnology, and Biochemistry, Vol.76, No.12, 2225-2229, 2012. (Summary) Osteoactivin is a type I transmembrane protein upregulated by unloading stresses, including denervation, prolonged bed rest, and space flight, but the regulatory mechanisms of its expression and activation under these conditions remain undefined. Here we report that osteoactivin protein exists in two forms: an intact transmembrane form and a secreted form. The secreted form, the extracellular fragment of osteoactivin, was produced by ectodomain shedding and was released into a culture medium. Amino acid sequence analysis of the carboxy-terminal fragment of osteoactivin (OA-CTF) revealed that cleavage of osteoactivin by proteases occurred both at the cell surface and within the cell membrane. Localization analysis demonstrated translocalization of OA-CTF to the nucleus and the endoplasmic reticulum. Moreover, RNA binding proteins, which regulate pre-mRNA splicing, were identified as OA-CTF binding proteins. These results suggest that OA-CTF formed by ectodomain shedding is involved in the regulation of pre-mRNA splicing. (Keyword) Active Transport, Cell Nucleus / Amino Acid Sequence / Animals / COS Cells / Cell Membrane / Cell Nucleus / Cercopithecus aethiops / Endoplasmic Reticulum / HEK293 Cells / Humans / Intracellular Space / Membrane Glycoproteins / Molecular Sequence Data / Peptide Fragments / Protein Binding / Protein Structure, Tertiary / Proteolysis / RNA-Binding Proteins (Tokushima University Institutional Repository) ● Metadata: 106158 (Link to Publication Site) ● Publication site (DOI): 10.1271/bbb.120515 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23221696 ● Search Scopus @ Elsevier (PMID): 23221696 ● Search Scopus @ Elsevier (DOI): 10.1271/bbb.120515 (Tokushima University Institutional Repository: 106158, DOI: 10.1271/bbb.120515, PubMed: 23221696)
65.	Rie Mukai, Hitomi Horikawa, Yutaka Fujikura, Tomoyuki Kawamura, Hisao Nemoto, Takeshi Nikawa and Junji Terao : Prevention of disuse muscle atrophy by dietary ingestion of 8-prenylnaringenin in denervated mice, PLoS ONE, Vol.7, No.9, e45048, 2012. (Summary) Flavonoids have attracted considerable attention in relation to their effects upon health. 8-Prenylnaringenin (8-PN) is found in the common hop (Humulus lupulus) and assumed to be responsible for the health impact of beer consumption. We wanted to clarify the effects of prenylation on the physiological functions of dietary flavonoids by comparing the effects of 8-PN with that of intact naringenin in the prevention of disuse muscle atrophy using a model of denervation in mice. Consumption of 8-PN (but not naringenin) prevented loss of weight in the gastrocnemius muscle further supported by the lack of induction of the protein content of a key ubiquitin ligase involved in muscle atrophy, atrogin-1, and by the activation of Akt phosphorylation. 8-PN content in the gastrocnemius muscle was tenfold higher than that of naringenin. These results suggested that, compared with naringenin, 8-PN was effectively concentrated into skeletal muscle to exert its preventive effects upon disuse muscle atrophy. It is likely that prenylation generates novel functions for 8-PN by enhancing its accumulation into muscle tissue through dietary intake. (Keyword) Animals / Cell Line / Chromatography, High Pressure Liquid / Diet / Flavanones / Humulus / Male / Mice / Mice, Inbred C57BL / Muscle Denervation / Muscle Fibers, Skeletal / Muscle, Skeletal / Muscular Atrophy / Muscular Disorders, Atrophic / Phosphorylation / Powders / Proto-Oncogene Proteins c-akt / Water (Tokushima University Institutional Repository) ● Metadata: 110158 (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0045048 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23028754 ● Search Scopus @ Elsevier (PMID): 23028754 ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0045048 (Tokushima University Institutional Repository: 110158, DOI: 10.1371/journal.pone.0045048, PubMed: 23028754)
66.	Toshihiko Nishisho, Kiminori Yukata, Yoshito Matsui, Tetsuya Matsuura, Kousaku Higashino, K Suganuma, Takeshi Nikawa and Natsuo Yasui : Angiogenesis and myogenesis in mouse tibialis anterior muscles during distraction osteogenesis: VEGF, its receptors, and myogenin genes expression., Journal of Orthopaedic Research, Vol.30, No.11, 1767-1773, 2012. (Summary) Angiogenesis and myogenesis occur in the surrounding skeletal muscles following distraction osteogenesis, but their molecular mechanisms remain unclear. The present study investigated morphological features of lengthened muscles and the time course change of vascular endothelial growth factor (VEGF), its receptors (VEGFR-1 and VEGFR-2) and myogenin gene expression profiles related to angiogenesis and myogenesis in tibialis anterior (TA) muscles with a mouse model of distraction osteogenesis, which involves 1 week of waiting period (latency phase), 2 weeks of intermittent distraction (distraction phase), and 5 weeks of remodeling period (consolidation phase). Macroscopic findings showed that lengthened TA muscles increased to approximately 42% longer and 10% heavier at the end of the process when compared to pre-surgery. During the distraction phase, VEGF and its receptors were induced in the vascular endothelial cells, myogenin-positive satellite cells and myocytes, and subsequently, capillary progression and myogenesis were increased. Real-time RT-PCR showed that Vegf, Vegfr-1, Vegfr-2, and myogenin genes expression was enhanced during the muscle lengthening. Vegf and Vegfr-1 were upregulated following the recession of angiogenesis at the consolidation phase. We conclude that upregulation of VEGF and its receptors by mechanical tension-stress could be involved in the process of angiogenesis and myogenesis in lengthened muscles. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. (Link to Publication Site) ● Publication site (DOI): 10.1002/jor.22136 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22528802 ● Search Scopus @ Elsevier (PMID): 22528802 ● Search Scopus @ Elsevier (DOI): 10.1002/jor.22136 (DOI: 10.1002/jor.22136, PubMed: 22528802)
67.	Shohei Kohno, Yui Yamashita, Tomoki Abe, Katsuya Hirasaka, Motoko Oarada, Ayako Ohno, Shigetada Teshima-Kondo, Akira Higashibata, Inho Choi, Edward M. Mills, Yuushi Okumura, Junji Terao and Takeshi Nikawa : Unloading stress disturbs muscle regeneration through perturbed recruitment and function of macrophages., Journal of Applied Physiology, Vol.112, No.10, 1773-1782, 2012. (Summary) Skeletal muscle is one of the most sensitive tissues to mechanical loading, and unloading inhibits the regeneration potential of skeletal muscle after injury. This study was designed to elucidate the specific effects of unloading stress on the function of immunocytes during muscle regeneration after injury. We examined immunocyte infiltration and muscle regeneration in cardiotoxin (CTX)-injected soleus muscles of tail-suspended (TS) mice. In CTX-injected TS mice, the cross-sectional area of regenerating myofibers was smaller than that of weight-bearing (WB) mice, indicating that unloading delays muscle regeneration following CTX-induced skeletal muscle damage. Delayed infiltration of macrophages into the injured skeletal muscle was observed in CTX-injected TS mice. Neutrophils and macrophages in CTX-injected TS muscle were presented over a longer period at the injury sites compared with those in CTX-injected WB muscle. Disturbance of activation and differentiation of satellite cells was also observed in CTX-injected TS mice. Further analysis showed that the macrophages in soleus muscles were mainly Ly-6C-positive proinflammatory macrophages, with high expression of tumor necrosis factor- and interleukin-1, indicating that unloading causes preferential accumulation and persistence of proinflammatory macrophages in the injured muscle. The phagocytic and myotube formation properties of macrophages from CTX-injected TS skeletal muscle were suppressed compared with those from CTX-injected WB skeletal muscle. We concluded that the disturbed muscle regeneration under unloading is due to impaired macrophage function, inhibition of satellite cell activation, and their cooperation. (Link to Publication Site) ● Publication site (DOI): 10.1152/japplphysiol.00103.2012 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22383511 ● Summary page in Scopus @ Elsevier: 2-s2.0-84862082145 (DOI: 10.1152/japplphysiol.00103.2012, PubMed: 22383511, Elsevier: Scopus)
68.	C U. Lago, S M. Nowinski, J E. Rundhaug, M E. Pfeiffer, K Kiguchi, Katsuya Hirasaka, X Yang, E M. Abramson, S B. Bratton, O Rho, R Colavitti, M A. Kenaston, Takeshi Nikawa, C Trempus, J Digiovanni, S M. Fischer and E M. Mills : Mitochondrial respiratory uncoupling promotes keratinocyte differentiation and blocks skin carcinogenesis., Oncogene, Vol.31, No.44, 4725-4731, 2012. (Summary) Decreased mitochondrial oxidative metabolism is a hallmark bioenergetic characteristic of malignancy that may have an adaptive role in carcinogenesis. By stimulating proton leak, mitochondrial uncoupling proteins (UCP1-3) increase mitochondrial respiration and may thereby oppose cancer development. To test this idea, we generated a mouse model that expresses an epidermal-targeted keratin-5-UCP3 (K5-UCP3) transgene and exhibits significantly increased cutaneous mitochondrial respiration compared with wild type (FVB/N). Remarkably, we observed that mitochondrial uncoupling drove keratinocyte/epidermal differentiation both in vitro and in vivo. This increase in epidermal differentiation corresponded to the loss of markers of the quiescent bulge stem cell population, and an increase in epidermal turnover measured using a bromodeoxyuridine (BrdU)-based transit assay. Interestingly, these changes in K5-UCP3 skin were associated with a nearly complete resistance to chemically-mediated multistage skin carcinogenesis. These data suggest that targeting mitochondrial respiration is a promising novel avenue for cancer prevention and treatment.Oncogene advance online publication, 23 January 2012; doi:10.1038/onc.2011.630. (Link to Publication Site) ● Publication site (DOI): 10.1038/onc.2011.630 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22266853 ● Summary page in Scopus @ Elsevier: 2-s2.0-84869083044 (DOI: 10.1038/onc.2011.630, PubMed: 22266853, Elsevier: Scopus)
69.	Shohei Kohno, Tatsuya Ueji, Tomoki Abe, Reiko Nakao, Katsuya Hirasaka, Motoko Oarada, Akiko Harada, Ayako Maita, Akira Higashibata, Rie Mukai, Junji Terao, Yuushi Okumura and Takeshi Nikawa : Rantes secreted from macrophages disturbs skeletal muscle regeneration after cardiotoxin injection in Cbl-b-deficient mice, Muscle & Nerve, Vol.43, No.2, 223-229, 2011. (Summary) Deficiency of the Cbl-b ubiquitin ligase gene activates macrophages in mice. This study aimed to elucidate the pathophysiological roles of macrophages in muscle degeneration/regeneration in Cbl-b-deficient mice. We examined immune cell infiltration and cytokine expression in cardiotoxin-injected tibialis anterior muscle of Cbl-b-deficient mice. Ablation of the Cbl-b gene expression delayed regeneration of cardiotoxin-induced skeletal muscle damage compared with wild-type mice. CD8-positive T cells were still present in the damaged muscle on day 14 after cardiotoxin injection in Cbl-b-deficient mice, but there was dispersal of the same cells over that time-frame in wild-type mice. Infiltrating macrophages in Cbl-b-deficient mice showed strong expression of RANTES (regulated-on-activation, normal T cell expressed and secreted), a chemokine for CD8-positive T cells. In turn, a neutralizing antibody against RANTES significantly suppressed the infiltration of CD8-positive T cells into the muscle, resulting in restoration of the disturbed muscle regeneration. Cbl-b is an important regulatory factor for cytotoxic T-cell infiltration via RANTES production in macrophages. (Keyword) Adaptor Proteins, Signal Transducing / analysis of variance / Animals / Antibodies / Antigens, CD / Cardiotoxins / Chemokine CCL5 / cytokinesis / Disease Models, Animal / Dose-Response Relationship, Drug / Gene Expression Regulation / Macrophages / Mice / Mice, Inbred C57BL / knockout mice / Muscle, Skeletal / Muscular Diseases / Myogenic Regulatory Factors / Proto-Oncogene Proteins c-cbl / RNA, Messenger / regeneration / Time Factors (Link to Publication Site) ● Publication site (DOI): 10.1002/mus.21829 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21254087 ● Summary page in Scopus @ Elsevier: 2-s2.0-78751674465 (DOI: 10.1002/mus.21829, PubMed: 21254087, Elsevier: Scopus)
70.	Rie Mukai, Reiko Nakao, Hironori Yamamoto, Takeshi Nikawa, Eiji Takeda and Junji Terao : Quercetin Prevents Unloading-Derived Disused Muscle Atrophy by Attenuating the Induction of Ubiquitin Ligases in Tail-Suspension Mice., Journal of Natural Products, Vol.73, No.10, 1708-1710, 2010. (Summary) The effects of quercetin (1) were investigated on disused muscle atrophy using mice that underwent tail suspension. Periodic injection of 1 into the gastrocnemius muscle suppressed muscle weight loss and ubiquitin ligase expression. Compound 1 reduced the enhancement of lipid peroxidation in the muscle. Injection of N-acetyl-l-cysteine, but not flavone (2), also prevented muscle weight loss and enhancement of lipid peroxidation. These findings demonstrate that 1 can prevent disused muscle atrophy by attenuating the expression of ubiquitin ligases and that such prevention originates from its antioxidant activity. (Link to Publication Site) ● Publication site (DOI): 10.1021/np100240y (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20853873 ● Search Scopus @ Elsevier (PMID): 20853873 ● Search Scopus @ Elsevier (DOI): 10.1021/np100240y (DOI: 10.1021/np100240y, PubMed: 20853873)
71.	Motoko Oarada, Miki Igarashi, Tsuyoshi Tsuzuki, Katsuhiko Kamei, Katsuya Hirasaka, Takeshi Nikawa, Teruo Miyazawa, Kiyotaka Nakagawa and Tohru Gonoi : Effects of a high-protein diet on host resistance to Paracoccidioides brasiliensis in mice, Bioscience, Biotechnology, and Biochemistry, Vol.74, No.3, 620-626, 2010. (Summary) We investigated the effects of high protein intake on host resistance to Paracoccidioides brasiliensis. Two-d fasted mice were infected with P. brasiliensis and refed on diets with three different levels (54%, 20%, and 5%) of casein. The mice refed the 54% casein diet showed reduced antifungal activity in the spleen and liver as compared with the mice refed the 5% or the 20% casein diet. After infection, increases in spleen and liver mRNA levels of myeloperoxidase, cathepsin-G, and elastase-2 were more profound in the mice refed the 54% casein diet as compared with the mice refed the 5% or the 20% casein diet. Infected mice refed the 54% casein diet exhibited greater interferon (IFN)-gamma production in the spleen and liver and higher levels of thiobarbituric acid reactive substances (TBARSs) in the liver as compared with those refed the 5% casein diet. These results indicate that high protein intake impairs host resistance to P. brasiliensis. (Keyword) Animals / Caseins / Cathepsin G / Dietary Proteins / Female / Host-Pathogen Interactions / Interferon-gamma / Liver / Mice / Mice, Inbred BALB C / Paracoccidioides / Paracoccidioidomycosis / Peroxidase / Serine Endopeptidases / Spleen / Thiobarbituric Acid Reactive Substances (Link to Publication Site) ● Publication site (DOI): 10.1271/bbb.90829 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20208341 ● Summary page in Scopus @ Elsevier: 2-s2.0-77950107302 (DOI: 10.1271/bbb.90829, PubMed: 20208341, Elsevier: Scopus)
72.	Motoko Oarada, Miki Igarashi, Tsuyoshi Tsuzuki, Nobuyuki Kurita, Tohru Gonoi, Takeshi Nikawa, Katsuya Hirasaka, Teruo Miyazawa, Kiyotaka Nakagawa and Katsuhiko Kamei : Effect of dietary oils on host resistance to fungal infection in psychologically stressed mice, Bioscience, Biotechnology, and Biochemistry, Vol.73, No.9, 1994-1998, 2009. (Summary) Psychological stress can modulate host defense against invading pathogens. In this study, we investigated the effect of dietary oils on social isolation stress-induced modulation of host resistance to Paracoccidioides brasiliensis. In olive oil-fed mice, 3 weeks of isolation stress resulted in temporarily delayed clearance of this fungus in the liver compared with group-housed mice. By contrast, in soybean oil-fed mice, isolation stress had no significant effect on antifungal activity. The olive oil-fed mice showed greater liver interferon (IFN)-gamma and interleukin (IL)-6 production in response to infection as compared with the soybean oil-fed mice. In the olive oil-fed mice, isolation stress led to greater infection-induced IFN-gamma production in the liver compared with the group-housed animals. These results indicate that the modulatory effects of psychological stress on host resistance to P. brasiliensis can vary depending on dietary fatty acid composition. (Keyword) Animals / Dietary Fats, Unsaturated / Female / Interferon-gamma / Interleukin-6 / Liver / Mice / Mice, Inbred BALB C / Mycoses / Organ Size / Social Isolation / Spleen / Stress, Psychological (Link to Publication Site) ● Publication site (DOI): 10.1271/bbb.90184 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19734677 ● Summary page in Scopus @ Elsevier: 2-s2.0-70349662151 (DOI: 10.1271/bbb.90184, PubMed: 19734677, Elsevier: Scopus)
73.	Motoko Oarada, Katsuhiko Kamei, Tohru Gonoi, Tsuyoshi Tsuzuki, Takahito Toyotome, Katsuya Hirasaka, Takeshi Nikawa, Ayaka Sato and Nobuyuki Kurita : Beneficial effects of a low-protein diet on host resistance to Paracoccidioides brasiliensis in mice, Nutrition, Vol.25, No.9, 954-963, 2009. (Summary) Although protein malnutrition impairs immune functions, several studies have recently shown that protein restriction without malnutrition is beneficial to host defenses against invading pathogens and cancer. In an effort to establish the optimum diet for host resistance, we investigated the effect of different dietary protein levels on host resistance to Paracoccidioides brasiliensis. Mice were fasted for 2 days and then infected with P. brasiliensis. Immediately after challenge with this fungus, mice were refed on diets with three different levels (0%, 1.5%, or 20%) of casein. On days 0-7 after infection, antifungal activity and levels of proinflammatory mediators in the spleen and liver were measured. Mice refed on the 1.5% casein diet showed higher antifungal activity in the spleen and liver compared with mice on the 20% casein diet. The antifungal activity in the spleens of mice refed on the 0% casein diet was intermediate between the antifungal activities of those refed the 1.5% and 20% casein diets. After infection, increases in spleen and liver levels of interleukin-6 and interferon-gamma, liver mRNA levels of antimicrobial proteins (myeloperoxidase, cathepsin-G, and elastase-2), and liver mRNA levels of proinflammatory mediators (interleukin-18, chemokine C-X-C motif ligand 10, nuclear factor-kappaB, inducible nitric oxide synthase, and granulocyte-macrophage colony-stimulating factor) were less profound in mice on the 1.5% or 0% casein diet compared with mice refed the 20% casein diet. The present results suggest that protein restriction without malnutrition could be beneficial to host resistance to P. brasiliensis. (Keyword) Animals / Caseins / Cathepsin G / Cathepsins / Diet, Protein-Restricted / Dose-Response Relationship, Drug / Female / gene expression / innate immunity / Interferon-gamma / Interleukin-6 / Liver / Mice / Mice, Inbred BALB C / Paracoccidioides / Paracoccidioidomycosis / Peroxidase / RNA, Messenger / Serine Endopeptidases / Spleen (Link to Publication Site) ● Publication site (DOI): 10.1016/j.nut.2009.02.004 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19403266 ● Summary page in Scopus @ Elsevier: 2-s2.0-67849124188 (DOI: 10.1016/j.nut.2009.02.004, PubMed: 19403266, Elsevier: Scopus)
74.	Reiko Nakao, Katsuya Hirasaka, Jumpei Goto, Kazumi Ishidoh, Chiharu Yamada, Ayako Ohno, Yuushi Okumura, Ikuya Nonaka, Koji Yasutomo, KM Baldwin, Eiki Kominami, Akira Higashibata, Keisuke Nagano, Keiji Tanaka, Natsuo Yasui, EM Mills, Shinichi Takeda and Takeshi Nikawa : Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading., Molecular and Cellular Biology, Vol.29, No.17, 4798-4811, 2009. (Summary) Skeletal muscle atrophy caused by unloading is characterized by both decreased responsiveness to myogenic growth factors (e.g., insulin-like growth factor 1 [IGF-1] and insulin) and increased proteolysis. Here, we show that unloading stress resulted in skeletal muscle atrophy through the induction and activation of the ubiquitin ligase Cbl-b. Upon induction, Cbl-b interacted with and degraded the IGF-1 signaling intermediate IRS-1. In turn, the loss of IRS-1 activated the FOXO3-dependent induction of atrogin-1/MAFbx, a dominant mediator of proteolysis in atrophic muscle. Cbl-b-deficient mice were resistant to unloading-induced atrophy and the loss of muscle function. Furthermore, a pentapeptide mimetic of tyrosine(608)-phosphorylated IRS-1 inhibited Cbl-b-mediated IRS-1 ubiquitination and strongly decreased the Cbl-b-mediated induction of atrogin-1/MAFbx. Our results indicate that the Cbl-b-dependent destruction of IRS-1 is a critical dual mediator of both increased protein degradation and reduced protein synthesis observed in unloading-induced muscle atrophy. The inhibition of Cbl-b-mediated ubiquitination may be a new therapeutic strategy for unloading-mediated muscle atrophy. (Keyword) Adaptor Proteins, Signal Transducing / Amino Acid Sequence / Animals / Cell Line / Forkhead Transcription Factors / Hindlimb Suspension / Humans / Insulin Receptor Substrate Proteins / Insulin-Like Growth Factor I / Male / Mice / Mice, Inbred C57BL / Mice, Knockout / Molecular Sequence Data / Muscle Proteins / Muscle, Skeletal / Muscular Atrophy / Oligopeptides / Proto-Oncogene Proteins c-cbl / Rats / Rats, Sprague-Dawley / SKP Cullin F-Box Protein Ligases / Signal Transduction / Space Flight / Ubiquitin (Link to Publication Site) ● Publication site (DOI): 10.1128/MCB.01347-08 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19546233 ● Search Scopus @ Elsevier (PMID): 19546233 ● Search Scopus @ Elsevier (DOI): 10.1128/MCB.01347-08 (DOI: 10.1128/MCB.01347-08, PubMed: 19546233)
75.	Ibrahim Dalia Ismaeil Hemdan, Katsuya Hirasaka, Reiko Nakao, Shohei Kohno, Sachiko Kagawa, Tomoki Abe, Akiko Harada, Yuushi Okumura, Yutaka Nakaya, Junji Terao and Takeshi Nikawa : Polyphenols prevent clinorotation-induced expression of atrogenes in mouse C2C12 skeletal myotubes., The Journal of Medical Investigation : JMI, Vol.56, No.1-2, 26-32, 2009. (Summary) Oxidative stress is a key factor in stimulating the expression of atrogenes, which are muscle atrophy-related ubiquitin ligases, in skeletal muscle, and it induces muscle atrophy during unloading. However, the effects of antioxidative nutrients on atrogene expression have not been demonstrated. We report on the inhibitory effects of polyphenols, such as epicatechin (EC), epicatechin gallate (ECg) and epigallocatechin gallate (EGCg) and quercetin, on atrogene expression up-regulated by three dimensional (3D)-clinorotation or glucocorticoid. These treatments markedly elevated the expression of atrogenes, including atrogin-1 and MuRF-1, in mouse C2C12 myoblasts and myotubes. Interestingly, EC, ECg, EGCg and quercetin significantly decreased the expression of atrogin-1 and MuRF-1 up-regulated by 3D-clinorotation, whereas they hardly affected atrogene expression induced by dexamethasone. ERK signaling is a well known MAPK pathway to mediate oxidative stress. Therefore, we also investigated the effect of these polyphenols on phosphorylation of ERK in C2C12 myotubes. As expected, EC, ECg, EGCg, and quercetin significantly suppressed phosphorylation of ERK, corresponding to the up-regulation of atrogenes induced by 3D-clinorotation. These results suggest that antioxidative nutrients, such as catechins and quercetin, suppress atrogene expression in skeletal muscle cells, possibly through the inhibition of ERK signaling. Thus, catechins and quercetin may prevent unloading-mediated muscle atrophy. (Keyword) Animals / Antioxidants / catechin / Cell Line / Dexamethasone / Extracellular Signal-Regulated MAP Kinases / flavonoids / Glucocorticoids / Mice / Muscle Fibers, Skeletal / Muscle Proteins / Muscle, Skeletal / oxidative stress / Phenols / oxidative phosphorylation / Quercetin / Rotation / SKP Cullin F-Box Protein Ligases / Ubiquitin-Protein Ligases (Tokushima University Institutional Repository) ● Metadata: 110881 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.56.26 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19262011 ● Summary page in Scopus @ Elsevier: 2-s2.0-63349112144 (Tokushima University Institutional Repository: 110881, DOI: 10.2152/jmi.56.26, PubMed: 19262011, Elsevier: Scopus)
76.	Mayumi Mikura, Ippei Yamaoka, Masako Doi, Yuichi Kawano, Mitsuo Nakayama, Reiko Nakao, Katsuya Hirasaka, Yuushi Okumura and Takeshi Nikawa : Glucose Infusion Suppresses Surgery-induced Muscle Protein Breakdown by Inhibiting Ubiquitin-proteasome Pathway in Rats, Anesthesiology, Vol.110, No.1, 81-88, 2009. (Summary) It appears to have been well established that after surgery, protein catabolism is accelerated and glucose infusion suppresses the catabolic reactions. However, in the early postoperative period, the effects of surgical stress and glucose infusion on muscle protein catabolism and the related mechanisms remain unclear. Rats undergoing laparotomy were infused with acetated Ringer's solution (10 ml x kg(-1) x h(-1)) without glucose (control) or containing 1% or 5% glucose. The infusion was continued for a further 4 h after the surgical treatment. The catabolic index, excretion of urinary nitrogen and 3-methylhistidine, and release of tyrosine and 3-methylhistidine from isolated muscle were determined. Furthermore, muscular mRNA expression of proteolytic-related genes (atrogin-1/MAFbx, muscle ring finger-1, mu- and m-calpain, and cathepsin L and H) and phosphorylation of components of insulin signaling (forkhead box O3 and protein kinase B) were evaluated. Surgery increased the catabolic index, and this increase was suppressed by glucose infusion (both 1% and 5%). In the control group, mRNA expression of atrogin-1/MAFbx and muscle ring finger-1 was increased, and they were suppressed in the two glucose groups. Furthermore, insulin signaling (phosphorylation of protein kinase B and forkhead box O3) in muscles was stimulated by glucose infusion. The present study indicates that glucose infusion, even at a relatively low rate, suppresses muscle protein breakdown in the early postoperative period. The mechanism of this effect is related to the suppression of the ubiquitin-proteasome pathway, accompanied by activation of insulin signaling. (Keyword) Animals / glucose / Infusions, Intravenous / Male / metabolism / Muscle Proteins / Muscle, Skeletal / Postoperative Complications / Proteasome Endopeptidase Complex / Rats / Rats, Sprague-Dawley / signal transduction / Ubiquitin (Link to Publication Site) ● Publication site (DOI): 10.1097/ALN.0b013e318190b6c1 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19104174 ● Summary page in Scopus @ Elsevier: 2-s2.0-58749093268 (DOI: 10.1097/ALN.0b013e318190b6c1, PubMed: 19104174, Elsevier: Scopus)
77.	Masuhiro Nishimura, Mayumi Mikura, Katsuya Hirasaka, Yuushi Okumura, Takeshi Nikawa, Yuichi Kawano, Mitsuo Nakayama and Muneharu Ikeda : Effects of dimethyl sulphoxide and dexamethasone on mRNA expression of myogenesis- and muscle proteolytic system-related genes in mouse myoblastic C2C12 cells, The Journal of Biochemistry, Vol.144, No.6, 717-724, 2008. (Summary) We examined the time course of mRNA expression of myogenic cell differentiation- and muscle proteolytic system-related genes in cultures of C2C12 cells during differentiation from myoblasts to myotubes. Furthermore, we treated C2C12 myotubes with dimethyl sulphoxide (DMSO) and dexamethasone (Dex), and examined changes in these mRNA levels. Myogenin (Myog), Atrogin1, forkhead box O1 (Foxo1) and Capn1 mRNA levels increased in C2C12 cells differentiating from myoblasts to myotubes, whereas Myf5 mRNA levels decreased. Although genes such as MRF4, Foxo3a, UbB, Capn1 and MuRF1 mRNAs in the myotubes were affected by DMSO exposure, mRNA levels of other genes were not markedly affected by exposure to 0.02% or 0.5% DMSO. Myf5, MRF4, Atrogin1, Foxo3 and MuRF1 mRNA levels were elevated by Dex at all time points, Cbl and Capn1 mRNA levels were significantly elevated by Dex at 8 h, and Myog mRNA levels were significantly elevated by Dex at 24 h. However, CtsH mRNA levels decreased significantly with Dex at 24 h. This study provides a useful database of gene profiles that are differentially expressed throughout myogenic cell differentiation and the muscle proteolytic system. (Keyword) Animals / cell differentiation / Cell Line / Dexamethasone / Dimethyl Sulfoxide / gene expression / Mice / Muscle Development / Muscle Fibers, Skeletal / RNA, Messenger (Link to Publication Site) ● Publication site (DOI): 10.1093/jb/mvn126 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18835828 ● Summary page in Scopus @ Elsevier: 2-s2.0-57749195680 (DOI: 10.1093/jb/mvn126, PubMed: 18835828, Elsevier: Scopus)
78.	Yuko Minami, Kyuichi Kawabata, Yoshiaki Kubo, Seiji Arase, Katsuya Hirasaka, Takeshi Nikawa, Noriko Bando, Yoshichika Kawai and Junji Terao : Peroxidized cholesterol-induced matrix metalloproteinase-9 activation and its suppression by dietary beta-carotene in photoaging of hairless mouse skin., The Journal of Nutritional Biochemistry, Vol.20, No.5, 389-398, 2008. (Summary) The activation of matrix metalloproteinase (MMP)-9 leading to the formation of wrinkle and sagging of skin is an essential step in the skin photoaging on exposure to ultraviolet A (UVA). This study attempted to elucidate the role of peroxidized cholesterol including cholesterol hydroperoxides (Chol-OOHs), primary products of lipid peroxidation in biomembranes, in MMP-9 activation and the effect of dietary beta-carotene in MMP-9 activation. Hairless mice were subjected to periodic UVA irradiation for 8 weeks. The amount of peroxidized cholesterol detected as total hydroxycholesterol in the skin was increased significantly by the exposure. The activity and protein level of MMP-9 were elevated with wrinkling and sagging formation. MMP-9 activity was also enhanced by the intracutaneous injection of Chol-OOHs into the mouse skin. Adding beta-carotene to the diet of the mice during the period of irradiation suppressed the activity and expression of MMP-9 as well as the wrinkling and sagging formation. The amount of cholesterol 5alpha-hydroperoxide, a singlet molecular oxygen oxygenation-specific peroxidized cholesterol, was significantly lowered by the addition of beta-carotene to the diet. These results strongly suggest that Chol-OOHs formed on exposure to UVA contribute to the expression of MMP-9, resulting in photoaging. Dietary beta-carotene prevents the expression of MMP-9, at least partly, by inhibiting photodynamic action involved in the formation of Chol-OOHs. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jnutbio.2008.04.010 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18656335 ● Search Scopus @ Elsevier (PMID): 18656335 ● Search Scopus @ Elsevier (DOI): 10.1016/j.jnutbio.2008.04.010 (DOI: 10.1016/j.jnutbio.2008.04.010, PubMed: 18656335)
79.	Yoshiko Nakae, Katsuya Hirasaka, J. Goto, Takeshi Nikawa, Masayuki Shono, M. Yoshida and PJ. Stowrd : Subcutaneous injection, from birth, of epigallocatechin-3-gallate, a component of green tea, limits the onset of muscular dystrophy in mdx mice: a quantitative histological, immunohistochemical and electrophysiological study., Histochemistry and Cell Biology, Vol.129, No.4, 489-501, 2008. (Summary) Dystrophic muscles suffer from enhanced oxidative stress. We have investigated whether administration of an antioxidant, epigallocatechin-3-gallate (EGCG), a component of green tea, reduces their oxidative stress and pathophysiology in mdx mice, a mild phenotype model of human Duchenne-type muscular dystrophy. EGCG (5 mg/kg body weight in saline) was injected subcutaneously 4x a week into the backs of C57 normal and dystrophin-deficient mdx mice for 8 weeks after birth. Saline was injected into normal and mdx controls. EGCG had almost no observable effects on normal mice or on the body weights of mdx mice. In contrast, it produced the following improvements in the blood chemistry, muscle histology, and electrophysiology of the treated mdx mice. First, the activities of serum creatine kinase were reduced to normal levels. Second, the numbers of fluorescent lipofuscin granules per unit volume of soleus and diaphragm muscles were significantly decreased by about 50% compared to the numbers in the corresponding saline-treated controls. Third, in sections of diaphragm and soleus muscles, the relative area occupied by histologically normal muscle fibres increased significantly 1.5- to 2-fold whereas the relative areas of connective tissue and necrotic muscle fibres were substantially reduced. Fourth, the times for the maximum tetanic force of soleus muscles to fall by a half increased to almost normal values. Fifth, the amount of utrophin in diaphragm muscles increased significantly by 17%, partially compensating for the lack of dystrophin expression. (Keyword) epigallocatechin-3-gallate / green tea / mdx mice / histological (Link to Publication Site) ● Publication site (DOI): 10.1007/s00418-008-0390-2 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18264714 ● Search Scopus @ Elsevier (PMID): 18264714 ● Search Scopus @ Elsevier (DOI): 10.1007/s00418-008-0390-2 (DOI: 10.1007/s00418-008-0390-2, PubMed: 18264714)
80.	Katsuya Hirasaka, Tokuoka Kaori, Nakao Reiko, Yamada Chiharu, Oarada Motoko, imagawa Takahiko, Ishidoh Kazumi, Yuushi Okumura, Kyoichi Kishi and Takeshi Nikawa : Cathepsin C propeptide interacts with intestinal alkaline phosphatase and heat shock cognate protein 70 in human Caco-2 cells, The Journal of Physiological Sciences, Vol.58, No.2, 105-111, 2008. (Summary) The oligomeric structure and the residual propeptide are distinct characteristics of cathepsin C from other members in the papain superfamily. In this study, we examined the physiological role of the cathepsin C propeptide. The stable overexpression of cathepsin C propeptide significantly decreased the activities of intestinal alkaline phosphatase (IAP) and sucrase in human Caco-2 intestinal epithelial cells, whereas it did not change the proliferation and cathepsin C activity. The overexpression of cathepsin C propeptide significantly decreased the amounts of IAP protein in differentiated Caco-2 cells, compared with the transfection of mock vector, whereas the amounts of IAP transcripts were not changed. Pulse-chase analysis confirmed that the reduction in IAP activity was due to an increase in IAP degradation, but not a decrease in IAP expression. For the mechanism of the enhanced IAP degradation, we identified proteins interacting with cathepsin C propeptide in Caco-2 cells by immunoprecipitation and mass spectrometry. Cathepsin C propeptide interacted with proteins with a molecular mass of approximately 70 kDa, including IAP and heat shock cognate protein 70. Our present results suggest that the propeptide of cathepsin C may stimulate the sorting to the lysosome, at least in part, contributing to the degradation of IAP in Caco-2 cells. (Keyword) Adenocarcinoma / Alkaline Phosphatase / Antigens, Neoplasm / Caco-2 Cells / Cathepsin C / Cathepsins / cell differentiation / Colonic Neoplasms / Enzyme Precursors / GPI-Linked Proteins / Gene Expression Regulation, Neoplastic / HSC70 Heat-Shock Proteins / Humans / Lysosomes / Sucrase (Link to Publication Site) ● Publication site (DOI): 10.2170/physiolsci.RP013007 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18307834 ● Summary page in Scopus @ Elsevier: 2-s2.0-43249114639 (DOI: 10.2170/physiolsci.RP013007, PubMed: 18307834, Elsevier: Scopus)
81.	Oarada Motoko, Tsuzuki Tsuyoshi, Gonoi Tohru, Igarashi Miki, Kamei Katsuhiko, Takeshi Nikawa, Katsuya Hirasaka, Ogawa Takayuki, Miyazawa Teruo, Nakagawa Kiyotaka and Kurita Nobuyuki : Effects of dietary fish oil on lipid peroxidation and serum triacylglycerol levels in psychologically stressed mice, Nutrition, Vol.24, No.1, 67-75, 2008. (Summary) The intake of omega-3 polyunsaturated fatty acids and psychological stress can each induce tissue lipid peroxidation. In our present study, we investigated their combined effects on the oxidative status of mouse tissues. Mice were group-housed (four mice/cage) and fed a diet containing fish oil (as a source of omega-3 polyunsaturated fatty acids), soybean oil, or olive oil for 3 wk. These animals were then 1) housed under the same conditions (four per cage, control group) or 2) individually housed to generate psychological stress conditions (isolation stress). After 2 wk of isolation stress, the levels of thiobarbituric acid-reactive substances (an index of lipid peroxidation) and antioxidants in the liver and kidney and the serum levels of triacylglycerol were measured. Fish oil-fed mice showed increased levels of thiobarbituric acid-reactive substances in their livers and kidneys compared with soybean oil- or olive oil-fed mice. These increases in thiobarbituric acid-reactive substance levels in the fish oil-fed mice were less profound under isolation stress conditions when compared with the group-housed animals on the same diet. In the fish oil-fed mice, isolation stress led to an increase in liver vitamin E levels when compared with their group-housed counterparts. The fish oil-fed mice exhibited lower serum triacylglycerol levels compared with the soybean oil- or olive oil-fed mice, and this decrease was more profound under conditions of isolation stress when compared with group-housing conditions. Dietary fish oil combined with isolation stress results in lower levels of lipid peroxidation in the liver and kidney compared with dietary fish oil alone. (Keyword) Animals / Antioxidants / Fatty Acids, Omega-3 / Female / Fish Oils / Kidney / lipid peroxidation / Liver / Mice / Mice, Inbred BALB C / oxidative stress / Plant Oils / Random Allocation / Soybean Oil / Stress, Psychological / Thiobarbituric Acid Reactive Substances / Triglycerides (Link to Publication Site) ● Publication site (DOI): 10.1016/j.nut.2007.10.006 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18070659 ● Summary page in Scopus @ Elsevier: 2-s2.0-36749006599 (DOI: 10.1016/j.nut.2007.10.006, PubMed: 18070659, Elsevier: Scopus)
82.	Katsuya Hirasaka, S Kohno, J Goto, H Furochi, Kazuaki Mawatari, Nagakatsu Harada, Toshio Hosaka, Yutaka Nakaya, K Ishidoh, Toshiyuki Obata, Yousuke Ebina, H Gu, S Takeda, Kyoichi Kishi and Takeshi Nikawa : Deficiency of Cbl-b gene enhances infiltration and activation of macrophages in adipose tissue and causes peripheral insulin resistance in mice., Diabetes, Vol.56, No.10, 2511-2522, 2007. (Summary) c-Cbl plays an important role in whole-body fuel homeostasis by regulating insulin action. In the present study, we examined the role of Cbl-b, another member of the Cbl family, in insulin action. C57BL/6 (Cbl-b(+/+)) or Cbl-b-deficient (Cbl-b(-/-)) mice were subjected to insulin and glucose tolerance tests and a hyperinsulinemic-euglycemic clamp test. Infiltration of macrophages into white adipose tissue (WAT) was assessed by immunohistochemistry and flow cytometry. We examined macrophage activation using co-cultures of 3T3-L1 adipocytes and peritoneal macrophages. Elderly Cbl-b(-/-) mice developed glucose intolerance and peripheral insulin resistance; serum insulin concentrations after a glucose challenge were always higher in elderly Cbl-b(-/-) mice than age-matched Cbl-b(+/+) mice. Deficiency of the Cbl-b gene significantly decreased the uptake of 2-deoxyglucose into WAT and glucose infusion rate, whereas fatty liver was apparent in elderly Cbl-b(-/-) mice. Cbl-b deficiency was associated with infiltration of macrophages into the WAT and expression of cytokines, such as tumor necrosis factor-alpha, interleukin-6, and monocyte chemoattractant protein (MCP)-1. Co-culture of Cbl-b(-/-) macrophages with 3T3-L1 adipocytes induced leptin expression and dephosphorylation of insulin receptor substrate 1, leading to impaired glucose uptake in adipocytes. Furthermore, Vav1, a key factor in macrophage activation, was highly phosphorylated in peritoneal Cbl-b(-/-) macrophages compared with Cbl-b(+/+) macrophages. Treatment with a neutralizing anti-MCP-1 antibody improved peripheral insulin resistance and macrophage infiltration into WAT in elderly Cbl-b(-/-) mice. Cbl-b is a negative regulator of macrophage infiltration and activation, and macrophage activation by Cbl-b deficiency contributes to the peripheral insulin resistance and glucose intolerance via cytokines secreted from macrophages. (Keyword) 3T3 Cells / Adaptor Proteins, Signal Transducing / Adipocytes / Adipose Tissue / Animals / Biological Transport / Blood Glucose / Coculture Techniques / Crosses, Genetic / Energy Metabolism / Flow Cytometry / Glucose / Glucose Intolerance / Glucose Tolerance Test / Homeostasis / Insulin / Insulin Resistance / Macrophage Activation / Mice / Mice, Inbred C57BL / Mice, Knockout / Proto-Oncogene Proteins c-cbl (Link to Publication Site) ● Publication site (DOI): 10.2337/db06-1768 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17601987 ● Search Scopus @ Elsevier (PMID): 17601987 ● Search Scopus @ Elsevier (DOI): 10.2337/db06-1768 (DOI: 10.2337/db06-1768, PubMed: 17601987)
83.	Shunji Nakano, Takuya Mishiro, Sigeyuki Takahara, Hhiromiti Yokoi, Daisuke Hamada, Kiminori Yukata, Yoichiro Takata, Tomohiro Goto, Hiroshi Egawa, Susumu Yasuoka, H Furouchi, Katsuya Hirasaka, Takeshi Nikawa and Natsuo Yasui : Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis., Clinical Rheumatology, Vol.26, No.8, 1284-1292, 2007. (Summary) The objective of this study is to examine the differential expression of mast cell tryptase and its receptor, protease-activated receptor-2 (PAR-2), in the synovium and synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Biochemical and immunohistochemical analyses were performed to determine whether the trypsin-like protease in the synovium is identical to mast cell tryptase. The effects of mast cell tryptase on the proliferation of synovial fibroblast-like cells (SFCs) and the release of IL-8 thereof were evaluated by the [3H]-thymidine incorporation and ELISA, respectively. The trypsin-like protease in the synovium of RA patients was identical to human mast cell tryptase, which was composed of two subunits: 33 and 34 kDa. The 33- and 34-kDa proteins are different glycosylated forms of the 31-kDa protein, which was unglycosylated. Mast cell tryptase activity in RA synovial fluid was significantly higher than that in OA synovial fluid, while their activities and expression in the synovium were similar. Expression of PAR-2 mRNA in the synovium was higher in RA than in OA. Mast cell tryptase containing the unglycosylated 31-kDa subunit was the predominant form in synovial fluid. RA patients had higher amounts of this subunit in their synovial fluid than OA patients. Mast cell tryptase and PAR-2 activating peptide stimulated the proliferation of SFCs and release of IL-8 from these cells. Mast cell tryptase secretion into RA synovial fluid is higher than OA synovial fluid. Mast cell tryptase in synovial fluid stimulates the proliferation of SFCs and the release of pro-inflammatory cytokines via PAR-2, which may contribute to exacerbation of synovitis in RA. (Keyword) Adult / Aged / Aged, 80 and over / Arthritis, Rheumatoid / Female / Humans / Knee Joint / Male / Middle Aged / Osteoarthritis / RNA, Messenger / Receptor, PAR-2 / Synovial Fluid / Synovial Membrane / Synovitis / Tryptases (Link to Publication Site) ● Publication site (DOI): 10.1007/s10067-006-0495-8 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17205215 ● Summary page in Scopus @ Elsevier: 2-s2.0-34447132817 (DOI: 10.1007/s10067-006-0495-8, PubMed: 17205215, Elsevier: Scopus)
84.	Takayuki Ogawa, Harumi Furochi, Mai Mameoka, Katsuya Hirasaka, Yuko Onishi, Naoto Suzue, Motoko Oarada, Motoki Aakamatsu, Hiroshi Akima, Tetsuo Fukunaga, Kyoichi Kishi, Natsuo Yasui, Kazumi Ishidoh, Hideoki Fukuoka and Takeshi Nikawa : Ubiquitin ligase gene expression in healthy volunteers with 20-day bedrest., Muscle & Nerve, Vol.34, No.4, 463-469, 2006. (Summary) In animal models, several ubiquitin ligases play an important role in skeletal muscle atrophy caused by unloading. In this study we examined protein ubiquitination and ubiquitin ligase gene expression in quadriceps femoris muscle from healthy volunteers after 20-day bedrest to clarify ubiquitin-dependent proteolysis in human muscles after unloading. During bedrest, thickness and cross-sectional area of the quadriceps femoris muscle decreased significantly by 4.6% and 3.7%, respectively. Ubiquitinated proteins accumulated in these atrophied human muscles. A real-time reverse transcription-polymerase chain reaction system showed that bedrest significantly upregulated expression of two ubiquitin ligase genes, Cbl-b and atrogin-1. We also performed DNA microarray analysis to examine comprehensive gene expression in the atrophied muscle. Bedrest mainly suppressed the expression of muscle genes associated with control of gene expression in skeletal muscle. Our results suggest that, in humans, Cbl-b- or atrogin-1-mediated ubiquitination plays an important role in unloading-induced muscle atrophy, and that unloading stress may preferentially inhibit transcriptional responses in skeletal muscle. (Keyword) Adaptor Proteins, Signal Transducing / Adult / Bed Rest / Body Weight / DNA / Gene Expression Profiling / Gene Expression Regulation, Enzymologic / Humans / Male / Muscle Proteins / Muscle, Skeletal / Muscular Atrophy / Oligonucleotide Array Sequence Analysis / Organ Size / Proteins / Proto-Oncogene Proteins c-cbl / SKP Cullin F-Box Protein Ligases / Ubiquitin-Protein Ligases (Link to Publication Site) ● Publication site (DOI): 10.1002/mus.20611 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16868939 ● Search Scopus @ Elsevier (PMID): 16868939 ● Search Scopus @ Elsevier (DOI): 10.1002/mus.20611 (DOI: 10.1002/mus.20611, PubMed: 16868939)
85.	Tadatoshi Sato, Hironori Yamamoto, Naoki Sawada, Kunitaka Nashiki, Mitsuyoshi Tsuji, Kazusa Muto, H Kume, Hajime Sasaki, Hidekazu Arai, Takeshi Nikawa, Yutaka Taketani and Eiji Takeda : Restraint stress alters the duodenal expression of genes important for lipid metabolism in rat., Toxicology, Vol.227, No.3, 248-261, 2006. (Summary) Stress, such as trauma and injury, is known to cause transcriptional changes in various tissues; however, there is little information on tissue-specific gene expression in response to stress. Here, we have examined duodenal gene expression in rats subjected to whole-body immobilization in order to elucidate the mechanism underlying the stress response in the duodenum--one of the tissues that is most sensitive to external stress. DNA microarray analysis revealed that the immobilization for 2 weeks caused great changes in gene expression in the rat duodenum: 165 genes exhibited more than a two-fold change in expression level (103 up-regulated; 62 down-regulated). In addition, functional classification of these genes showed that immobilization preferentially stimulated the expression of genes related to lipid metabolism, including genes encoding mitochondrial HMG-CoA synthase, a key enzyme in ketogenesis; solute carrier 27A2, a fatty acid transporter; and dienoyl CoA reductase, a key enzyme in beta-oxidation. To elucidate the factors mediating these immobilization-induced changes, we treated rats and small intestinal IEC-6 cells with dexamethasone and hydrogen peroxide. In both rats and IEC-6 cells, treatment with dexamethasone induced changes in gene expression that mimicked the immobilization-mediated increase in expression of the mitochondrial HMG-CoA synthase and dienoyl CoA reductase transcripts, suggesting that stress-induced synthesis of glucocorticoid hormones mediates, at least in part, the stress response in the duodenum. These results suggest that immobilization may alter lipid metabolism in the small intestine by modifying the expression of specific genes through which the small intestine may seek to protect itself from stress-induced damage. (Keyword) Animals / Cell Line / Dexamethasone / Down-Regulation / Duodenum / Gene Expression / Hydrogen Peroxide / Lipid Metabolism / Male / Mitochondria / Oligonucleotide Array Sequence Analysis / Rats / Rats, Wistar / Restraint, Physical / Reverse Transcriptase Polymerase Chain Reaction / Stress, Psychological / Up-Regulation (Link to Publication Site) ● Publication site (DOI): 10.1016/j.tox.2006.08.009 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16962226 ● Search Scopus @ Elsevier (PMID): 16962226 ● Search Scopus @ Elsevier (DOI): 10.1016/j.tox.2006.08.009 (DOI: 10.1016/j.tox.2006.08.009, PubMed: 16962226)
86.	Rie Shimooka, Yasuhiro Kido, Naoko Chiba, Junko Tanaka, Kazuhito Rokutan, Harumi Furochi, Katsuya Hirasaka, Takeshi Nikawa and Kyoichi Kishi : Soy protein diet prevents hypermethioninemia caused by portacaval shunt in rats., The Journal of Medical Investigation : JMI, Vol.53, No.3-4, 255-263, 2006. (Summary) In hepatic disorders, abnormal plasma amino acid profiles are observed. In this study, we examined whether soy protein isolate (SPI) improved plasma methionine concentration in the model animals. Portacaval shunt (PCS) increased alanine aminotransferase (ALT) activity and methionine concentration in blood of rats fed a 40% casein diet supplemented with 0.6% methionine (casein-M diet). A 40% SPI diet supplemented with 1.28% methionine (SPI-M diet), which contained the same amount of methionine as that in 40% casein-M diet, normalized plasma ALT activity and methionine level in PCS rats. These effects of a SPI diet may be due to its amino acid composition, since an amino acid mixture diet mimicking a 40% SPI-M diet was also effective to hypermethioninemia of PCS rats. To find key enzymes for the beneficial effect of soy protein, we examined effects of a 40% SPI-M or casein-M diet on the activities of three methionine-metabolizing enzymes in liver of PCS rats. A SPI-M diet stimulated only the activity of cystathionine gamma-lyase, compared with a casein-M diet. A SPI diet has a preventive effect on hypermethioninemia, at least in part, by stimulating cystathionine gamma-lyase activity in liver and may be used for nutritional management of liver disorders with hypermethioninemia. (Keyword) Alanine Transaminase / Animals / Caseins / Cystathionine / Dietary Proteins / Dietary Supplements / Liver Diseases / male / Metabolic Diseases / Methionine / Portacaval Shunt, Surgical / Rats / Rats, Wistar / Soybean Proteins (Tokushima University Institutional Repository) ● Metadata: 110820 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.53.255 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16953062 ● CiNii @ National Institute of Informatics (CRID): 1390001204245200128 ● Search Scopus @ Elsevier (PMID): 16953062 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.53.255 (Tokushima University Institutional Repository: 110820, DOI: 10.2152/jmi.53.255, PubMed: 16953062, CiNii: 1390001204245200128)
87.	Tadatoshi Sato, Hironori Yamamoto, Naoki Sawada, Kunitaka Nashiki, Mitsuyoshi Tsuji, Takeshi Nikawa, Hidekazu Arai, Kyoko Morita, Yutaka Taketani and Eiji Takeda : Immobilization decreases duodenal calcium absorption through a 1,25-dihydroxyvitamin D-dependent pathway., Journal of Bone and Mineral Metabolism, Vol.24, No.4, 291-299, 2006. (Summary) Immobilization induces significant and progressive bone loss, with an increase in urinary excretion and a decrease in intestinal absorption of calcium. These actions lead to negative calcium balance and the development of disuse osteoporosis. The aims of this study were to evaluate the molecular mechanisms of decreased intestinal calcium absorption and to determine the effect of dietary 1,25-dihydroxyvitamin D [1,25(OH)2D] and a high-calcium diet on bone loss due to immobilization. The immobilized rat model was developed in the Bollman cage III to induce systemic disuse osteoporosis in the animals. There was a significant decrease in lumbar bone mineral density (BMD) and intestinal calcium absorption in the immobilized group compared with the controls. Serum 25-hydroxyvitamin D concentration did not change, but 1,25(OH)2D concentration decreased significantly. The mRNA levels of renal 25-hydoxyvitamin D 24-hydroxylase (24OHase) increased, whereas those of renal 25-hydroxyvitamin D 1-alpha hydroxylase (1alpha-hydroxylase), duodenal transient receptor potential cation channel, subfamily V, member 6 (TRPV6), TRPV5, and calbindin-D9k were all decreased. A high-calcium diet did not prevent the reduction in lumbar BMD or affect the mRNA expression of proteins related to calcium transport. Dietary administration of 1,25(OH)2D increased the intestinal calcium absorption that had been downregulated by immobilization. TRPV6, TRPV5, and calbindin-D9k mRNA levels were also upregulated, resulting in prevention of the reduction in lumbar BMD. Therefore, it is concluded that dietary 1,25(OH)2D prevented decreases in intestinal calcium absorption and simultaneously prevented bone loss in immobilized rats. However, it remains unclear that calcium absorption and expression of calcium transport proteins are essential for the regulation of lumbar BMD. (Keyword) Animals / Calcium / Calcium, Dietary / Dihydroxycholecalciferols / Duodenum / Humans / Immobilization / Intestinal Absorption / Rats / Rats, Wistar (Link to Publication Site) ● Publication site (DOI): 10.1007/s00774-006-0686-z (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16816923 ● Search Scopus @ Elsevier (PMID): 16816923 ● Search Scopus @ Elsevier (DOI): 10.1007/s00774-006-0686-z (DOI: 10.1007/s00774-006-0686-z, PubMed: 16816923)
88.	Naoto Suzue, Takeshi Nikawa, Yuko Onishi, Chiharu Yamada, Katsuya Hirasaka, Takayuki Ogawa, Harumi Furochi, Hirofumi Kosaka, Kazumi Ishidoh, Gu Hua, Shin'ichi Takeda, Naozumi Ishimaru, Yoshio Hayashi, Hironori Yamamoto, Kyoichi Kishi and Natsuo Yasui : Ubiqitin Ligase Cbl-b Downregulates Bone Formation Through Suppression of IGF-I Signaling in Osteoblasts During Denervation, Journal of Bone and Mineral Research, Vol.21, No.5, 722-734, 2006. (Summary) Unloading can prevent bone formation by osteoblasts. To study this mechanism, we focused on a ubiquitin ligase, Cbl-b, which was highly expressed in osteoblastic cells during denervation. Our results suggest that Cbl-b may mediate denervation-induced osteopenia by inhibiting IGF-I signaling in osteoblasts. Unloading, such as denervation (sciatic neurectomy) and spaceflight, suppresses bone formation by osteoblasts, leading to osteopenia. The resistance of osteoblasts to growth factors contributes to such unloading-mediated osteopenia. However, a detailed mechanism of this resistance is unknown. We first found that a RING-type ubiquitin ligase, Cbl-b, was highly expressed in osteoblastic cells after sciatic neurectomy in mice. In this study, we reasoned that Cbl-b played an important role in the resistance of osteoblasts to IGF-I. Cbl-b-deficient (Cbl-b(-/-)) or wildtype (Cbl-b(+/+)) mice were subjected to sciatic neurectomy. Bone formation in these mice was assessed by calcein labeling and histomorphometric analyses. We examined IGF-I signaling molecules in femora of these mice by Western blot and immunohistochemical analyses. We also examined the mitogenic response of Cbl-b-overexpressing or -deficient osteoblastic cells to various growth factors. In Cbl-b(+/+) mice, denervation decreased femur mass and bone formation, whereas it increased the expression of Cbl-b protein in osteoprogenitor cells and in osteocalcin-positive cells (osteoblastic cells) in hindlimb bone. In contrast, in Cbl-b(-/-) mice, bone mass and bone formation were sustained during denervation. Denervation inhibited the mitogenic response of osteoprogenitor cells most significantly to IGF-I. Therefore, we focused on Cbl-b-mediated modification of IGF-I signaling. Denervation decreased the amounts of insulin receptor substrate-1 (IRS-1), phosphatidly inositol 3-phosphate kinase (PI3K), and Akt-1 proteins in femora of Cbl-b(+/+) mice, whereas the amounts of these IGF-I signaling molecules in femora of Cbl-b(-/-) mice were constant after denervation. On a cellular level, primary osteoblastic cells from Cbl-b(-/-) mice were more stimulated to proliferate by IGF-I treatment compared with those from Cbl-b(+/+) mice. Furthermore, overexpression of Cbl-b increased ubiquitination and degradation of IRS-1 in primary Cbl-b(-/-) osteoblastic cells, leading to their impaired mitogenic response to IGF-I. These results suggest that Cbl-b induces resistance of osteoblasts to IGF-I during denervation by increasing IRS-1 degradation and that Cbl-b-mediated modification of IGF-I signaling may contribute to decreased bone formation during denervation. (Keyword) Animals / Base Sequence / Blotting, Western / Bone Development / Cells, Cultured / DNA Primers / Denervation / Down-Regulation / Hydrolysis / immunohistochemistry / Insulin-Like Growth Factor I / Mice / Mice, Inbred C57BL / Osteoblasts / Protein Binding / Reverse Transcriptase Polymerase Chain Reaction / signal transduction / Ubiquitin / Ubiquitin-Protein Ligases (Link to Publication Site) ● Publication site (DOI): 10.1359/jbmr.060207 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16734387 ● Summary page in Scopus @ Elsevier: 2-s2.0-33646227897 (DOI: 10.1359/jbmr.060207, PubMed: 16734387, Elsevier: Scopus)
89.	Harumi Furochi, Takeshi Nikawa, Katsuya Hirasaka, Naoto Suzue, Kazumi Ishidoh, Yuko Onishi, Takahiro Ogawa, Chiharu Yamada, Hiromi Suzuki, Akira Higashibata, Motoko Oarada, Kyoichi Kishi and Natsuo Yasui : Distinct gene expression profiles in the femora of rats exposed to spaceflight, tail-suspension and dnervation., Biological Sciences in Space, Vol.20, No.3, 80-90, 2006. (Keyword) Denervation / Microarray analysis / Rat femora / Spaceflight / Tail-suspension (Link to Publication Site) ● Publication site (DOI): 10.2187/bss.20.80 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520572357921133952 ● Search Scopus @ Elsevier (DOI): 10.2187/bss.20.80 (DOI: 10.2187/bss.20.80, CiNii: 1520572357921133952)
90.	Yuko Onishi, Katsuya Hirasaka, Ibuki Ishihara, Motoko Oarada, Jumpei Goto, Takayuki Ogawa, Naoto Suzue, Shunji Nakano, Harumi Furochi, Kazumi Ishidoh, Kyoichi Kishi and Takeshi Nikawa : Identification of mono-ubiquitinated LDH-A in skeletal muscle cells exposed to oxidative stress, Biochemical and Biophysical Research Communications, Vol.336, No.3, 799-806, 2005. (Summary) We previously reported that oxidative stress is associated with unloading-mediated ubiquitination of muscle proteins. To further elucidate the involvement of oxidative stress in ubiquitination, we examined the ubiquitination profile in rat myoblastic L6 cells after treatment with hydrogen peroxide. Hydrogen peroxide induced many ubiquitinated proteins with low molecular masses (less than 60 kDa) as well as high molecular masses (more than 160 kDa). Among them, a 42-kDa-ubiquitinated protein was abundantly accumulated and immediately disappeared after the treatment. Microsequencing revealed that the 42-kDa-protein was identical to the mono-ubiquitinated form of rat lactate dehydrogenase A (LDH-A), and we confirmed that hydrogen peroxide induced the mono-ubiquitination of LDH-A in COS7 cells overexpressing LDH-A and ubiquitin. Under unloading conditions, such as tail-suspension and spaceflight, mono-ubiquitinated LDH was accumulated in gastrocnemius muscle. Interestingly, E-64-d plus pepstatin, lysosomal protease inhibitors, further accumulated mono-ubiquitinated LDH-A in the cells after treatment with hydrogen peroxide, while they did not affect the amount of poly-ubiquitinated LDH. In contrast, epoxomicin, a potent proteasome inhibitor, did not change the amount of mono-ubiquitinated LDH-A in L6 cells treated with hydrogen peroxide, although it significantly increased the amount of poly-ubiquitinated LDH. Our results suggest that oxidative stress induces not only poly-ubiquitination but also mono-ubiquitination of LDH-A, which may be involved in its lysosomal degradation during unloading. (Keyword) Animals / COS Cells / Cell Line / Cercopithecus aethiops / hydrogen peroxide / Isoenzymes / L-Lactate Dehydrogenase / Muscle, Skeletal / oxidative stress / Phosphoglycerate Mutase / Protease Inhibitors / Protein Processing, Post-Translational / Ubiquitins / Weightlessness (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2005.08.175 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16154111 ● Search Scopus @ Elsevier (PMID): 16154111 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2005.08.175 (DOI: 10.1016/j.bbrc.2005.08.175, PubMed: 16154111)
91.	Takayuki Ogawa, Takeshi Nikawa, Harumi Furochi, Miki Kosyoji, Katsuya Hirasaka, Naoto Suzue, Koichi Sairyo, Shunji Nakano, Takashi Yamaoka, Mitsuo Itakura, Kyoichi Kishi and Natsuo Yasui : Osteoactivin upregulates expression of MMP-3 and MMP-9 in fibroblasts infiltrated into denervated skeletal muscle in mice, American Journal of Physiology, Cell Physiology, Vol.289, No.3, C697-C707, 2005. (Summary) In this study, we examined pathophysiological roles of osteoactivin, a functionally unknown type I membrane glycoprotein, in mouse skeletal muscle atrophied by denervation (sciatic neurectomy). Denervation increased the amounts of osteoactivin, vimentin, matrix metalloproteinase-3 (MMP-3), and MMP-9 in mouse gastrocnemius muscle. Interestingly, immunohistochemical analysis revealed that vimentin, MMP-3, and MMP-9 were mainly present in fibroblast-like cells infiltrated into denervated mouse gastrocnemius muscle, whereas osteoactivin was expressed in the sarcolemma of myofibers adjacent to the fibroblast-like cells. On the basis of these findings, we reasoned that osteoactivin in myocytes was involved in activation of the infiltrated fibroblasts. To address this issue, we examined effects of osteoactivin on expression of MMPs in fibroblasts in vitro and in vivo. Overexpression of osteoactivin in NIH-3T3 fibroblasts induced expression of MMP-3, but not in mouse C(2)C(12) myoblasts, indicating that osteoactivin might functionally target fibroblasts. Treatment with recombinant mouse osteoactivin increased the amounts of collagen type I, MMP-3, and MMP-9 in mouse NIH-3T3 fibroblasts. The upregulated expression of these fibroblast marker proteins was significantly inhibited by heparin, but not by an integrin inhibitor, indicating that a heparin-binding motif in the extracellular domain might be an active site of osteoactivin. In osteoactivin-transgenic mice, denervation further enhanced expression of MMP-3 and MMP-9 in fibroblasts infiltrated into gastrocnemius muscle, compared with wild-type mice. Our present results suggest that osteoactivin might function as an activator for fibroblasts infiltrated into denervated skeletal muscles and play an important role in regulating degeneration/regeneration of extracellular matrix. (Keyword) sciatic neurectomy / Gpnmb family / C2C12 cells / NIH-3T3 cells / osteoactivin-transgenic mice (Link to Publication Site) ● Publication site (DOI): 10.1152/ajpcell.00565.2004 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16100390 ● Search Scopus @ Elsevier (PMID): 16100390 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpcell.00565.2004 (DOI: 10.1152/ajpcell.00565.2004, PubMed: 16100390)
92.	Katsuya Hirasaka, Takeshi Nikawa, Louis Yuge, Ibuki Ishihara, Akira Higashibata, Noriaki Ishioka, Atsuko Okubo, Takashi Miyashita, Naoto Suzue, Takayuki Ogawa, Motoko Oarada and Kyoichi Kishi : Clinorotation prevents differentiation of rat myoblastic L6 cells in association with reduced NF-κB signaling, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol.1743, No.1-2, 130-140, 2005. (Summary) In this study, we examined effects of the three-dimensional (3D)-clinorotation, a simulated-model of microgravity, on proliferation/differentiation of rat myoblastic L6 cells. Differentiation of L6 cells into myotubes was significantly disturbed in the 3D-clinorotation culture system, although the 3D-clinorotation had no effect on the proliferation. The 3D-clinorotation also suppressed the expression of myogenesis marker proteins, such as myogenin and myosin heavy chain (MHC), at the mRNA level. In association with this reduced differentiation, we found that the 3D-clinorotation prevented accumulation of ubiquitinated proteins, compared with non-rotation control cells. Based on these findings, we focused on the ubiquitin-dependent degradation of I kappa B, a myogenesis inhibitory protein, to clarify the mechanism of this impaired differentiation. A decline in the amount of I kappa B protein in L6 cells was significantly prevented by the rotation, while the amount of the protein in the non-rotated cells decreased along with the differentiation. Furthermore, the 3D-clinorotation reduced the NF-kappaB-binding activity in L6 cells and prevented the ubiquitination of I kappa B proteins in the I kappa B- and ubiquitin-expressing Cos7 cells. Other myogenic regulatory factors, such as deubiquitinases, cyclin E and oxygen, were not associated with the differentiation impaired by the clinorotation. Our present results suggest that simulated microgravity such as the 3D-clinorotation may disturb skeletal muscle cell differentiation, at least in part, by inhibiting the NF-kappa B pathway. (Keyword) Animals / Blotting, Western / COS Cells / cell differentiation / Cell Line / Cell Line, Tumor / Cyclin E / I-kappa B Proteins / Immunoblotting / Immunoprecipitation / Muscle Fibers, Skeletal / Muscle, Skeletal / Muscles / Myogenin / Myosin Heavy Chains / NF-kappa B / Oxygen / RNA, Messenger / Rats / Reverse Transcriptase Polymerase Chain Reaction / signal transduction / Time Factors / Transfection / Ubiquitin / Weightlessness (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbamcr.2004.09.013 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15777848 ● Search Scopus @ Elsevier (PMID): 15777848 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbamcr.2004.09.013 (DOI: 10.1016/j.bbamcr.2004.09.013, PubMed: 15777848)
93.	Katsuya Hirasaka, Takeshi Nikawa, Yuki Asanoma, Harumi Furochi, Yuko Onishi, Takayuki Ogawa, Naoto Suzue, Motoko Oarada, Toru Shimazu and Kyoichi Kishi : Short-term hypergravity does not affect protein-ubiquitination and proliferation in rat L6 myoblastic cells, Biological Sciences in Space, Vol.19, No.1, 3-7, 2005. (Summary) We previously reported that spaceflight (STS-90) and tail-suspension stimulated muscle protein ubiquitination and accumulated the degradation fragments. However, in space experiments the side-effects of hypergravity on samples are inevitable during the launch of a space shuttle into space or the reentry. To examine whether hypergravity also caused protein-ubiquitination in skeletal muscle cells, we exposed rat myoblastic L6 cells to various hypergravity conditions. Immunoblot analysis showed that the centrifugation at 2, 3, 30 or 100 G for 10 min did not increase the amount of ubiquitinated proteins in L6 cells, whereas the centrifugation at 100 G for 1 or 2 hrs significantly induced the protein-ubiquitination. In contrast, heat shock protein 70 (HSP70), another stress-responsive protein, in L6 cells was accumulated only by centrifugation at 100 G for more than 10 min. Short-term (10 min) hypergravity including 3 or 100 G did not affect the proliferation and morphological changes in L6 cells. Our present results suggest that the ubiquitination of muscle proteins is less sensitive to hypergravity than the induction of HSP70, and that the effect of hypergravity on protein-ubiquitination and proliferation of skeletal muscle cells may be negligible, as far as its duration is short-term. (Keyword) hypergravity / ubiquitination / HSP70 / rat myoblastic L6 cells (Link to Publication Site) ● Publication site (DOI): 10.2187/bss.19.3 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16118477 ● CiNii @ National Institute of Informatics (CRID): 1390001204433381120 ● Search Scopus @ Elsevier (PMID): 16118477 ● Search Scopus @ Elsevier (DOI): 10.2187/bss.19.3 (DOI: 10.2187/bss.19.3, PubMed: 16118477, CiNii: 1390001204433381120)
94.	Takuya Mishiro, Shunji Nakano, Shigeyuki Takahara, Mari Miki, Yoichi Nakamura, Susumu Yasuoka, Takeshi Nikawa and Natsuo Yasui : Relationship Between Cathepsin B and Thrombin in Rheumatoid Arthritis, The Journal of Rheumatology, Vol.31, No.7, 1265-1273, 2004. (Summary) To investigate the pathophysiological significance of cathepsin B and thrombin in synovial fluid (SF) from patients with rheumatoid arthritis (RA). Thrombin and cathepsin B activities of samples from patients with RA and osteoarthritis (OA) were measured using fluorogenic synthetic substrates. The concentration of interleukin 8 (IL-8) in SF was measured by ELISA. The effect of thrombin on the proliferation of synovial fibroblast-like cells (SFC) was examined by measuring 3H-thymidine incorporation. The effect of thrombin on the release of IL-8 and cathepsin B from SFC was investigated. The expression of IL-8 mRNA in SFC after stimulation with thrombin was evaluated using real-time quantitative RT-PCR. The effect of recombinant IL-8 on the activation of cathepsin B was examined using the knee joints of rabbits. In SF supernatants, cathepsin B and thrombin-like activity was significantly higher in RA than in OA, and there was a significant correlation between them. Cathepsin B activity was also significantly higher in SF cells and synovial tissue extracts from RA patients than in those from OA patients. There was a significant correlation between cathepsin B activity and the concentration of IL-8 in RA SF. Thrombin enhanced the proliferation of SFC in a dose-dependent manner. Thrombin significantly enhanced the release of IL-8 from SFC as well as the expression of IL-8 mRNA in SFC. IL-8 induced activation of cathepsin B in the knee joints of rabbits. However, thrombin did not directly increase cathepsin B activity in SFC. In RA, thrombin was found to be related to the enhanced growth of SFC and the release of IL-8 from these cells; thus thrombin is probably related to worsening of inflammation through the recruitment of leukocytes (neutrophils), which release cathepsin B into the SF. Thrombin can induce activation of cathepsin B in SFC via increased expression of IL-8. (Keyword) RHEUMATOID ARTHRITIS / CATHEPSIN B / THROMBIN / INTERLEUKIN 8 / NEUTROPHIL / SYNOVIAL FIBROBLAST-LIKE CELL (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15229942 ● Summary page in Scopus @ Elsevier: 2-s2.0-3042811556 (PubMed: 15229942, Elsevier: Scopus)
95.	Takeshi Nikawa, Kazumi Ishidoh, Katsuya Hirasaka, Ibuki Ishihara, Madoka Ikemoto, Mihoko kano, Eiki Kominami, Ikuya Nonaka, Takayuki Ogawa, Gregory R. Adams, kenneth M. Baldwin, Natsuo Yasui, Kyoichi Kishi and Shinichi Takeda : Skeletal muscle gene expression in space-flown rats, The FASEB journal, Vol.18, No.3, 522-524, 2004. (Summary) Skeletal muscles are vulnerable to marked atrophy under microgravity. This phenomenon is due to the transcriptional alteration of skeletal muscle cells to weightlessness. To further investigate this issue at a subcellular level, we examined the expression of approximately 26,000 gastrocnemius muscle genes in space-flown rats by DNA microarray analysis. Comparison of the changes in gene expression among spaceflight, tail-suspended, and denervated rats revealed that such changes were unique after spaceflight and not just an extension of simulated weightlessness. The microarray data showed two spaceflight-specific gene expression patterns: 1) imbalanced expression of mitochondrial genes with disturbed expression of cytoskeletal molecules, including putative mitochondria-anchoring proteins, A-kinase anchoring protein, and cytoplasmic dynein, and 2) up-regulated expression of ubiquitin ligase genes, MuRF-1, Cbl-b, and Siah-1A, which are rate-limiting enzymes of muscle protein degradation. Distorted expression of cytoskeletal genes during spaceflight resulted in dislocation of the mitochondria in the cell. Several oxidative stress-inducible genes were highly expressed in the muscle of spaceflight rats. We postulate that mitochondrial dislocation during spaceflight has deleterious effects on muscle fibers, leading to atrophy in the form of insufficient energy provision for construction and leakage of reactive oxygen species from the mitochondria. (Keyword) Adaptor Proteins, Signal Transducing / Animals / Animals, Newborn / Carrier Proteins / Denervation / Gene Expression Profiling / Gene Expression Regulation / Hindlimb Suspension / Male / Mitochondria, Muscle / Muscle Proteins / Muscle, Skeletal / Muscular Atrophy / Nuclear Proteins / Phosphoproteins / Proto-Oncogene Proteins c-cbl / Rats / Rats, Sprague-Dawley / Space Flight / Transcription, Genetic / Ubiquitin-Protein Ligases (Link to Publication Site) ● Publication site (DOI): 10.1096/fj.03-0419fje (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14715702 ● Summary page in Scopus @ Elsevier: 2-s2.0-2442701924 (DOI: 10.1096/fj.03-0419fje, PubMed: 14715702, Elsevier: Scopus)
96.	Louis Yuge, Atsuko Okubo, Takashi Miyashita, Takanori Kumagai, Takeshi Nikawa, Shinichi Takeda, Masamoto Kanno, Yukio Urabe, Masanori Sugiyama and Katsuko Kataoka : Physical stress by magnetic force accelerates differentiation of human osteoblasts, Biochemical and Biophysical Research Communications, Vol.311, No.1, 32-38, 2003. (Summary) We examined the effect of magnetic force on differentiation of cultured human osteoblasts. Magnetic microparticles (MPs) were introduced into the cytoplasm of a human osteoblast cell line and the cells were cultured in a magnetic field (MF) in group MP-MF. Three groups of controls were used: cells without MPs were cultured out of MF (group C), cells without MPs were cultured in MF (group MF), and cells with MPs were cultured out of MF (group MP). The cells in group MP-MF became larger and were elongated along the axis of the magnetic poles. Appearance of alkaline phosphatase (AlPase) activity, formation of bone nodules, and calcium deposition were accelerated depending on the intensity of the magnetic field. It takes longer culture in the other three groups to exhibit these changes. Core-binding factor A1 (Cbfa1: transcription factor for osteoblast differentiation) and osteocalcin (a bone-matrix protein involved in controlling osteogenesis) were expressed earlier or stronger in group MP-MF than the other groups. Then we compared phosphorylation of mitogen-activated protein kinase (MAPK) between group MP-MF and group C. Phosphorylation of p38(MAPK) (p38) was increased in group MP-MF, while total p38 as well as total and phosphorylated forms of MAPK/ERK 1/2 and SAPK/JNK were not changed between the two groups. When a p38 inhibitor, SB 203580, was added to the culture medium in group C, AlPase activity, formation of bone nodules, and calcium deposits were completely inhibited. On the other hand, they were inhibited only partially by a MAPK/ERK 1/2 inhibitor, U-0126. Based on these results, it is concluded that (1) osteoblast differentiation is accelerated by a magnetic force, (2) this acceleration is mainly attributed to the activation of p38 phosphorylation, and (3) the stimulus induced by a magnetic field offers a new approach to osteoblast differentiation. (Keyword) Calcification, Physiologic / Cell Differentiation / Cell Survival / Cells, Cultured / Core Binding Factor Alpha 1 Subunit / Core Binding Factors / Humans / Magnetics / Mechanotransduction, Cellular / Micromanipulation / Microspheres / Mitogen-Activated Protein Kinases / Neoplasm Proteins / Osteoblasts / Osteocalcin / Osteogenesis / Phosphorylation / Physical Stimulation / Stress, Mechanical / Transcription Factors / Weight-Bearing / p38 Mitogen-Activated Protein Kinases (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2003.09.156 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14575691 ● Search Scopus @ Elsevier (PMID): 14575691 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2003.09.156 (DOI: 10.1016/j.bbrc.2003.09.156, PubMed: 14575691)
97.	Motoko Oarada, Tsuyoshi Tsuzuki, Toshihide Suzuki, Teruo Miyazawa, Takeshi Nikawa, Guan Hong-quan and Nobuyuki Kurita : Dietary supplementation with docosahexaenoic acid, but not with eicosapentaenoic acid, reduces host resistance to fungal infection in mice, Biochimica et Biophysica Acta (BBA) - General Subjects, Vol.1622, No.3, 151-160, 2003. (Summary) The effect of dietary docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on host resistance to Paracoccidioides brasiliensis infection was investigated. Mice fed palm oil supplemented with DHA showed reduced antifungal activity in the spleen and liver, as compared with mice fed palm oil or soybean oil without supplementation with DHA. Mice fed DHA-supplemented soybean oil also showed reduced antifungal activity in the liver, but the extent of reduction was less profound. This reduction in antifungal activity was not observed with EPA-supplemented palm or EPA-supplemented soybean oil. These results suggest that two factors, DHA and palm oil in combination, are involved in reducing the host resistance. DHA-enriched palm oil was also responsible for an increase in DHA concentration and a marked decrease in arachidonic acid content in the spleen and liver. However, this group did not show elevated spleen and liver phospholipid hydroperoxide levels compared with the other groups, excluding the possibility that the reduction in antifungal activity observed with DHA-enriched palm oil is due to acceleration of in vivo lipid peroxidation. Greater infection-induced increases in spleen and serum interferon-gamma concentrations were observed in mice fed DHA-enriched palm oil compared with the other groups. (Keyword) Animals / Cytokines / Dietary Supplements / Docosahexaenoic Acids / Eicosapentaenoic Acid / Female / Immunity, Innate / Lipid Peroxidation / Liver / Mice / Mice, Inbred BALB C / Organ Size / Paracoccidioidomycosis / Phospholipids / Spleen (Link to Publication Site) ● Publication site (DOI): 10.1016/S0304-4165(03)00136-3 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12928111 ● Search Scopus @ Elsevier (PMID): 12928111 ● Search Scopus @ Elsevier (DOI): 10.1016/S0304-4165(03)00136-3 (DOI: 10.1016/S0304-4165(03)00136-3, PubMed: 12928111)
98.	Mihoko Kano, Takako Kitano, Madoka Ikemoto, Katsuya Hirasaka, Yuki Asanoma, Takayuki Ogawa, Shinichi Takeda, Ikuya Nonaka, Gregory R. Adams, Kenneth M. Baldwin, Motoko Oarada, Kyoichi Kishi and Takeshi Nikawa : Isolation and characterization of a novel gene sfig in rat skeletal muscle up-regulated by spaceflight (STS-90), The Journal of Medical Investigation : JMI, Vol.50, No.1-2, 39-47, 2003. (Summary) We obtained the skeletal muscle of rats exposed to weightless conditions during a 16-day-spaceflight (STS-90). By using a differential display technique, we identified 6 up-regulated and 3 down-regulated genes in the gastrocnemius muscle of the spaceflight rats, as compared to the ground control. The up-regulated genes included those coding Casitas B-lineage lymphoma-b, insulin growth factor binding protein-1, titin and mitochondrial gene 16 S rRNA and two novel genes (function unknown). The down-regulated genes included those encoding RNA polymerase II elongation factor-like protein, NADH dehydrogenase and one novel gene (function unknown). In the present study, we isolated and characterized one of two novel muscle genes that were remarkably up-regulated by spaceflight. The deduced amino acid sequence of the spaceflight-induced gene (sfig) comprises 86 amino acid residues and is well conserved from Drosophila to Homo sapiens. A putative leucine-zipper structure located at the N-terminal region of sfig suggests that this gene may encode a transcription factor. The up-regulated expression of this gene, confirmed by Northern blot analysis, was observed not only in the muscles of spaceflight rats but also in the muscles of tail-suspended rats, especially in the early stage of tail-suspension when gastrocnemius muscle atrophy initiated. The gene was predominantly expressed in the kidney, liver, small intestine and heart. When rat myoblastic L6 cells were grown to 100% confluence in the cell culture system, the expression of sfig was detected regardless of the cell differentiation state. These results suggest that spaceflight has many genetic effects on rat skeletal muscle. (Keyword) Amino Acid Sequence / Animals / Base Sequence / Cell Line / DNA, Complementary / Gene Expression Profiling / Gene Expression Regulation / Immobilization / Leucine Zippers / Male / Molecular Sequence Data / Muscle Proteins / Muscle, Skeletal / Organ Specificity / Rats / Rats, Wistar / Sequence Homology, Amino Acid / Space Flight / Species Specificity / Subtraction Technique / Tail / Transcription Factors (Tokushima University Institutional Repository) ● Metadata: 110676 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12630567 ● Summary page in Scopus @ Elsevier: 2-s2.0-0037762735 (Tokushima University Institutional Repository: 110676, PubMed: 12630567, Elsevier: Scopus)
99.	Madoka Ikemoto, Yoshihito Okamura, Mihoko Kano, Katsuya Hirasaka, Reiko Tanaka, Taeko Yamamoto, Takahiro Sasa, Takayuki Ogawa, Koichi Sairyo, Kyoichi Kishi and Takeshi Nikawa : A Relative High Dose of Vitamin E Does Not Attenuate Unweighting-Induced Oxidative Stress and Ubiquitination in Rat Skeletal Muscle, Journal of Physiological Anthropology and Applied Human Science, Vol.21, No.5, 257-263, 2002. (Summary) We previously reported that intragastric administration of cysteine could be beneficial to prevent unweighting-induced ubiquitination and degradation of muscle protein in association with redox regulation [Ikemoto et al., Biol. Chem., 383 (2002), 715-721]. In this study, we investigated whether vitamin E, another potent antioxidative nutrient, also had beneficial effects on the muscle protein catabolism. However, daily intragastric supplementation of 1.5 or 15 mg/rat of alpha-tocopherol did not prevent weight loss of hindlimb skeletal muscle in tail-suspended rats. To elucidate the reason for the non-effectiveness of vitamin E, we further examined concentrations of oxidative stress markers, ubiquitination of muscle proteins and fragmentation of myosin heavy chain in gastrocnemius muscle of rats daily treated with 15 mg of alpha-tocopherol. Unexpectedly, vitamin E increased concentrations of glutathione disulfide and thiobarbituric acid-reactive substance and decreased glutathione level in the muscle, compared with those of vehicle treatment, indicating that vitamin E enhanced unweighting-induced oxidative stress in skeletal muscle. The vitamin E supplementation did not suppress the ubiquitination of muscle proteins and fragmentation of myosin heavy chain caused by tail-suspension. Our results suggest that supplementation of a relative high dose of vitamin E could not inhibit ubiquitin-dependent degradation of muscle protein in tail-suspended rats possibly due to its prooxidant action. (Keyword) Animals / Blotting, Western / Cysteine Endopeptidases / Glutathione / Glutathione Disulfide / Hindlimb Suspension / immunohistochemistry / Male / Multienzyme Complexes / Muscle Proteins / Muscle, Skeletal / Myosin Heavy Chains / oxidative stress / Proteasome Endopeptidase Complex / Rats / Rats, Wistar / Thiobarbituric Acid Reactive Substances / Ubiquitin / Vitamin E (Link to Publication Site) ● Publication site (DOI): 10.2114/jpa.21.257 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12491823 ● Search Scopus @ Elsevier (PMID): 12491823 ● Search Scopus @ Elsevier (DOI): 10.2114/jpa.21.257 (DOI: 10.2114/jpa.21.257, PubMed: 12491823)
100.	Motoko Oarada, Takeshi Nikawa and Nobuyuki Kurita : Effect of timing of food deprivation on host resistance to fungal infection in mice, British Journal of Nutrition, Vol.88, No.2, 151-158, 2002. (Summary) Mice were deprived of food for a period of 72 h at varying times relative to the time of infection with Paracoccidioides brasiliensis. Host resistance was diminished profoundly when the period of food deprivation was from 48 h before to 24 h after infection (group B). When food deprivation was initiated immediately after infection (group C), host resistance was reduced less profoundly. When food deprivation was initiated at 24 and 48 h post-infection, reductions in host resistance were only moderate or not observed respectively. These results suggest that the earlier in the course of infection starvation occurs, the more profoundly host resistance is impaired. When food deprivation was initiated 72 h before infection, finishing at the time of infection (group A), the reduction in host resistance was considerably less profound compared with group B mice, suggesting that refeeding initiated immediately after infection is responsible for rapid restoration of the antifungal resistance in starved mice. Infection-induced responses of corticosterone and interferon-gamma were changed according to the timing of food deprivation. Group A mice, similar to non-fasted controls, showed an infection-induced increase in serum corticosterone concentration, while groups B and C did not. Group C mice showed a substantially greater infection-induced increase in serum interferon-gamma compared with the other fasted and non-fasted control groups. (Keyword) Acute Disease / Adrenocorticotropic Hormone / Animals / Corticosterone / Female / Food Deprivation / Immunity, Innate / Interferon-gamma / Mice / Mice, Inbred BALB C / Paracoccidioides / Paracoccidioidomycosis / Specific Pathogen-Free Organisms / Time Factors (Link to Publication Site) ● Publication site (DOI): 10.1079/BJNBJN2002600 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12144718 ● Search Scopus @ Elsevier (PMID): 12144718 ● Search Scopus @ Elsevier (DOI): 10.1079/BJNBJN2002600 (DOI: 10.1079/BJNBJN2002600, PubMed: 12144718)
101.	Takeshi Nikawa, Madoka Ikemoto, Takashi Sakai, Mihoko Kano, Takako Kitano, Tsukasa Kawahara, Shigetada Teshima, Kazuhito Rokutan and Kyoichi Kishi : Effects of a Soy Protein Diet on Exercise-Induced Muscle Protein Catabolism in Rats, Nutrition, Vol.18, No.6, 490-495, 2002. (Summary) We examined effects of dietary soy protein isolate on muscle calpain activity and myosin heavy chain (MHC) degradation in rats performing an acute running exercise. In rats fed a 20% casein diet, the treadmill running exercise, fixed at 80 kg/m, transiently increased calpain activity in gastrocnemius muscles in parallel with the release of creatine kinase into plasma. The fixed running also caused an accumulation of immunoreactive degradation fragments of MHC in the muscle. Feeding a 20% soy protein isolate diet as opposed to the control casein diet to rats significantly suppressed the running-induced activation of mu- and m-calpains, fragmentation of MHC, and release of creatine kinase into plasma (P < 0.05). Rats fed the soy protein isolate diet had significantly higher calpastatin activity in gastrocnemius muscle than did rats fed the casein diet (P < 0.05), indicating that this increase inhibits the exercise-induced autoactivation of calpain. Activities of proteasome, cathepsin B + L, and antioxidant enzymes and the levels of glutathione and thiobarbituric acid-reactive substances in the muscle did not differ between the diet groups at the end of the exercise. Our results suggest that diets containing soy protein prevent exercise-induced protein degradation in skeletal muscle, possibly through inhibiting the calpain-mediated proteolysis. (Keyword) soy protein isolate / treadmill running / calpain / myosin heavy chain / creatine kinase (Link to Publication Site) ● Publication site (DOI): 10.1016/S0899-9007(02)00744-X (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12044822 ● Summary page in Scopus @ Elsevier: 2-s2.0-0036274434 (DOI: 10.1016/S0899-9007(02)00744-X, PubMed: 12044822, Elsevier: Scopus)
102.	Takeshi Nikawa, Madoka Ikemoto, Chiho Watanabe, Takako Kitano, Mihoko Kano, Makoto Yoshimoto, Takae Towatari, Nobuhiko Katunuma, Fujiko Shizuka and Kyoichi Kishi : A Cysteine Protease Inhibitor Prevents Suspension-Induced Declines in Bone Weight and Strength in Rats, Journal of Physiological Anthropology and Applied Human Science, Vol.21, No.1, 51-57, 2002. (Summary) In this study, we examined the effects of a potent cysteine protease inhibitor, N-(L-3-trans-carboxyoxirane-2-cabonyl)-L-leucine-4-aminobutylamide (E-64a), on bone weight and strength in tail-suspended rats. We first administered a vehicle or 4 or 8 mg/rat of E-64a to rats fed with a low calcium diet for 7 wks to determine effective doses of E-64a on bone resorption in vivo. Femoral cathepsin K-like activity and serum hydroxyproline level in rats fed with a low calcium diet were significantly higher than those in rats fed with a standard diet. The intraperitoneal injection of 8 mg/rat of E-64a to rats decreased their serum calcium and hydroxyproline concentrations after 3 to 6 hrs in parallel with changes in femoral cathepsin K-like activity, while 4 mg/rat of E-64a had weaker effects on these parameters. Based on these results, we injected 8 mg/rat of E-64a to tail-suspended rats twice a day for 2 wks and compared the results with those of treatment with 1 mg/rat of etidronate, a bisphosphonate, twice a week. In tail-suspended rats, femoral weight and strength, assessed by three-point bending test, significantly decreased from Day 5 to 21, while femoral cathepsin K-like activity and serum calcium and hydroxyproline concentrations did not change. E-64a inhibited femoral cathepsin K-like activity in tail-suspended rats, but etidronate did not. E-64a as well as etidronate significantly prevented the suspension-induced declines in bone weight and strength. However, more frequent injection and higher doses were required for E-64a to exhibit significant efficacy of antiresorption, compared with those of etidronate. Our results suggest that a cysteine protease inhibitor could improve suspension-induced osteopenia by inhibiting cathepsin K-like activity in bone; however, it needs several improvements in the effect as a clinical drug. (Keyword) Animals / Bone Resorption / Bone and Bones / Calcium / Cathepsin K / Cathepsins / Collagenases / Cysteine Proteinase Inhibitors / Etidronic Acid / Femur / Hydroxyproline / Leucine / Male / Organ Size / Rats / Rats, Wistar / Weightlessness (Link to Publication Site) ● Publication site (DOI): 10.2114/jpa.21.51 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11938609 ● Search Scopus @ Elsevier (PMID): 11938609 ● Search Scopus @ Elsevier (DOI): 10.2114/jpa.21.51 (DOI: 10.2114/jpa.21.51, PubMed: 11938609)
103.	Tsukasa Kawahara, Yuki Kuwano, Shigetada Kondo, Tomoko Kawai, Takeshi Nikawa, Kyoichi Kishi and Kazuhito Rokutan : Toll-like receptor 4 regulates gastric pit cell responses to Helicobacter pylori infection, The Journal of Medical Investigation : JMI, Vol.48, No.3,4, 190-197, 2001. (Summary) Gastric pit cells express mitogen oxidase1 (Mox1) and essential components for the phagocyte NADPH oxidase (p67-, p47-, p40-, and p22-phoxes). Helicobacter pylori (Hp) lipopolysaccharide (LPS) is a potent up-regulator of the Mox 1 oxidase. In this study, we examined the expression levels of several key members of the Toll-like receptor (TLR) family in primary cultures of guinea pig gastric pit cells. These cells expressed the TLR4 mRNA. Immunoblot analysis and immunofluorescence histochemistry with an anti-TLR4 antibody showed that gastric pit cells possessed significant amounts of TLR4 protein preferentially on the plasma membrane. In contrast, the cells did not express the TLR2 and TLR9 transcripts and did not contain detectable amounts of TLR2 protein. Neither peptidoglycan from Staphylococcus aureus nor Hp DNA with the CpG motif up-regulated Mox1 oxidase activity. Hp LPS activated nuclear factor-kappa B in association with the expression of cyclooxygenase II and tumor necrosis factor alpha transcripts. These findings suggest that TLR4 may play a crucial role in the initiation of inflammatory responses of gastric pit cells against Hp infection. (Keyword) toll-like receptor / gastric pit cell / Helicobacter pylori / mitogen oxidase 1 (Tokushima University Institutional Repository) ● Metadata: 30592 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11694959 ● Search Scopus @ Elsevier (PMID): 11694959 (Tokushima University Institutional Repository: 30592, PubMed: 11694959)
104.	Tsukasa Kawahara, Yuki Kuwano, Shigetada Kondo, Toshiro Sugiyama, Tomoko Kawai, Takeshi Nikawa, Kyoichi Kishi and Kazuhito Rokutan : Helicobacter pylori lipopolysaccharide from type 1, but not type 2 strains, stimulates apoptosis of cultured gastric mucosal cells, The Journal of Medical Investigation : JMI, Vol.48, No.3,4, 167-174, 2001. (Summary) The cag pathogenicity island (cag PAI) genes are a major determinant of virulence of Helicobacter pylori (Hp). Lipopolysaccharide (LPS) purified from the cag PAI-positive (type I) strains induced apoptosis of primary cultures of guinea pig gastric mucosal cells. Lipid A catalyzed this apoptosis. These cells expressed the Toll-like receptor 4 (TLR4) mRNA and its protein, and type I Hp LPS phosphorylated transforming growth factor beta-activated kinase 1 (TAK1) and TAK1-binding protein 1 (TAB1) in association with up-regulation of the TLR4 expressions, suggesting that type I Hp LPS evoked distinct TLR4 signaling. In contrast, Hp LPS from type II strains with complete or partial deletion of the cag PAI genes did not phosphorylate TAK1 and TAB1 and failed to induce apoptosis. Accelerated apoptosis of gastric epithelial cells is one of the important events relevant to chronic, atrophic gastritis caused by Hp infection. The difference in proapoptotic action of LPS between the type I and II strains may support an important role of the cag PAI genes in the pathogenesis of gastric lesions caused by Hp infection. (Keyword) apoptosis / Helicobacter pylori / cag PAI gene / LPS / gastric mucosal cells (Tokushima University Institutional Repository) ● Metadata: 83815 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11694956 ● Search Scopus @ Elsevier (PMID): 11694956 (Tokushima University Institutional Repository: 83815, PubMed: 11694956)
105.	Takeshi Nikawa, Madoka Ikemoto, Mihoko Kano, Kaori Tokuoka, Katsuya Hirasaka, Shoji Uehara, Kiyoshi Takatsu, Kazuhito Rokutan and Kyoichi Kishi : Impaired Vitamin A-Mediated Mucosal IgA Response in IL-5 Receptor-Knockout Mice, Biochemical and Biophysical Research Communications, Vol.285, No.2, 546-549, 2001. (Summary) To clarify actions of vitamin A on mucosal immunity associated with interleukin-5 (IL-5), we examined effects of vitamin A on mucosal IgA level in IL-5 receptor alpha-chain-knockout (IL-5Ralpha(-/-)) mice. Daily supplementation of retinyl acetate (1 mg/mouse) increased Th2 cytokine levels and a number of their positive cells in the small intestinal mucosa of IL-5Ralpha(-/-) mice, as observed in wild-type or IL-5Ralpha(+/-) mice. Wild-type and heterozygous mice increased the IgA level and a number of IgA-containing cells in the mucosa in response to the vitamin A treatment, but not in IL-5Ralpha(-/-) mice. Retinyl acetate increased anti-cholera toxin (CT) IgA level in the mucosa of wild-type mice, improving their survival rate after an exposure to 0.4 mg of CT. However, retinyl acetate failed to induce resistance to CT toxicity in IL-5Ralpha(-/-) mice. Our results suggest that IL-5 may play an important role in an action of vitamin A on mucosal IgA system. (Keyword) vitamin A / IgA / IL-4 / IL-5 / IL-6 / small intestinal mucosa / IL-5 receptor α-chain-deficient mice / cholera toxin (Link to Publication Site) ● Publication site (DOI): 10.1006/bbrc.2001.5138 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11444878 ● Summary page in Scopus @ Elsevier: 2-s2.0-0034811765 (DOI: 10.1006/bbrc.2001.5138, PubMed: 11444878, Elsevier: Scopus)
106.	Madoka Ikemoto, Takeshi Nikawa, Shinichi Takeda, Chiho Watanabe, Takako Kitano, Baldwin M. Kenneth, Ryutaro Izumi, Ikuya Nonaka, Takae Towatari, Shigetada Teshima, Kazuhito Rokutan and Kyoichi Kishi : Space Shuttle flight (STS-90) enhances dagradation of rat myosin heavy chain in association with activation of ubiquitin-proteasome pathway, The FASEB journal, Vol.15, No.7, 1279-1281, 2001. (Keyword) Animals / Calpain / Cathepsin L / Cathepsins / Cysteine Endopeptidases / Cysteine Proteinase Inhibitors / Endopeptidases / Enzyme Precursors / Hindlimb Suspension / Leucine / Ligases / Models, Biological / Multienzyme Complexes / Muscle, Skeletal / Muscular Atrophy / Myosin Heavy Chains / Proteasome Endopeptidase Complex / RNA, Messenger / Rats / Reverse Transcriptase Polymerase Chain Reaction / Space Flight / Ubiquitins / Weightlessness / Weightlessness Simulation (Link to Publication Site) ● Publication site (DOI): 10.1096/fj.00-0629fje (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11344113 ● Summary page in Scopus @ Elsevier: 2-s2.0-0035348487 (DOI: 10.1096/fj.00-0629fje, PubMed: 11344113, Elsevier: Scopus)
107.	Takeshi Nikawa, Madoka Ikemoto, Kaori Tokuoka, Shigetada Teshima, Alpers H. David, Yoshihiro Masui, Kyoichi Kishi and Kazuhito Rokutan : Interleukin-1β enhances retinoic acid-mediated expression of bone-type alkaline phosphatase in rat IEC-6 cells, American Journal of Physiology, Gastrointestinal and Liver Physiology, Vol.280, No.3, 510-517, 2001. (Summary) We previously showed that vitamin A upregulated the expression of bone-type alkaline phosphatase (ALP) in fetal rat small intestine and rat intestinal IEC-6 cells. In this study, we examined interactions between retinoic acid (RA) and several growth factors/cytokines on the isozyme expression in IEC-6 cells. Epidermal growth factor and interleukins (ILs)-2, -4, -5, and -6 completely blocked the RA-mediated increase in ALP activity. In contrast, IL-1beta markedly increased the activity, protein, and mRNA of the bone-type ALP only when RA was present. IL-1beta and/or RA did not change the type 1 IL-1 receptor transcript level, whereas IL-1beta enhanced the RA-induced expressions of retinoic acid receptor-beta (RAR-beta) and retinoid X receptor-beta (RXR-beta) mRNAs and RA-mediated RXR response element binding. The synergism of IL-1beta and RA on ALP activity was completely blocked by protein kinase C (PKC) inhibitors. Our results suggest that IL-1beta may modify the ALP isozyme expression in small intestinal epithelial cells by stimulating PKC-dependent, RAR-beta- and/or RXR-beta-mediated signaling pathways. (Keyword) Alkaline Phosphatase / Animals / Bone and Bones / Cell Line / DNA-Binding Proteins / Drug Synergism / Enzyme Inhibitors / Epidermal Growth Factor / Interleukin-1 / Interleukin-2 / Interleukin-4 / Interleukin-5 / Interleukin-6 / Intestine, Small / Isoenzymes / Protein Kinase C / RNA, Messenger / Rats / Receptors, Retinoic Acid / Transcriptional Activation / Tretinoin (Link to Publication Site) ● Publication site (DOI): 10.1152/ajpgi.2001.280.3.g510 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11171635 ● Summary page in Scopus @ Elsevier: 2-s2.0-0035000306 (DOI: 10.1152/ajpgi.2001.280.3.g510, PubMed: 11171635, Elsevier: Scopus)
108.	Takeshi Nikawa, Kenji Odahara, Hiroyuki Koizumi, Yasuhiro Kido, Shigetada Teshima, Kazuhito Rokutan and Kyoichi Kishi : Vitamin A Prevents the Decline in Immunoglobulin A and Th2 Cytokine Levels in Small Intestinal Mucosa of Protein-Malnourished Mice1, Biochemical and Molecular Action of Nutrients, Vol.129, 934-941, 1999. (Keyword) vitamin A / protein-malnutrition / Immunoglobulin A / Th2 cytokine / mice
109.	Shigetada Teshima, Kazuhito Rokutan, Takeshi Nikawa and Kyoichi Kishi : Macrophage Colony-Stimulating Factor Stimulates Synthesis and Secretion of a Mouse Homolog of a Human IgE-Dependent Histamine-Releasing Factor by Macrophages In Vitro and In Vivo, The Journal of Immunology, Vol.161, No.11, 6356-6366, 1998.
110.	Shigetada Kondo, Kazuhito Rokutan, Takeshi Nikawa and Kyoichi Kishi : Macrophage colony-stimulating factor stimulates synthesis and secretion of a mouse homolog of a human IgE-dependent histamine-releasing factor by macrophages in vitro and in vivo., The Journal of Immunology, Vol.161, No.11, 6356-6366, 1998. (Summary) Treatment of murine resident peritoneal macrophages with macrophage-CSF (M-CSF) up-regulated the synthesis of a discrete set of proteins, including a 26-kDa protein (p26). The sequence of 20 NH2-terminal amino acids of the purified p26 was identical with the mouse homolog of a human IgE-dependent histamine-releasing factor (HRF). Among macrophage activators tested (M-CSF, granulocyte-macrophage-CSF, IL-3, TNF-alpha, IFN-gamma, and LPS), only M-CSF could up-regulate the p26 HRF synthesis by cultured macrophages. M-CSF not only increased the levels of p26 HRF mRNA and protein, but also stimulated the secretion of an N-glycosylated p26 HRF with a m.w. of 30 kDa. Repeated injections of M-CSF into mouse peritoneal cavity for 4 days elicited macrophages expressing abundant p26 HRF. A single i.p. injection of M-CSF failed to increase the p26 HRF level in peritoneal macrophages of thioglycollate-, LPS-, or adjuvant-treated mice, while M-CSF challenge to OVA-immunized mice caused macrophage infiltration and overproduction of p26 HRF, similarly as did OVA challenge. The Ag-specific priming for enhanced synthesis and secretion of p26 HRF by M-CSF was also demonstrated in cultured macrophages prepared from OVA-immunized mice. An i.p. injection of M-CSF or recombinant p26 HRF triggered eosinophil recruitment, even in the absence of the Ag, in the sensitized mice, but not in normal mice. Furthermore, recombinant p26 HRF could induce eosinophilia without marked macrophage and lymphocyte infiltrations. Our results suggest that p26 HRF secreted by M-CSF-stimulated macrophages may be an important mediator for the late phase allergic inflammation. (Keyword) Animals / Antigens / Biomarkers, Tumor / Cell Movement / cell separation / Cells, Cultured / Cycloheximide / Eosinophils / Histamine Release / Humans / Immunoglobulin E / Injections, Intraperitoneal / Lipopolysaccharides / Lymphokines / Macrophage Colony-Stimulating Factor / Macrophages, Peritoneal / Mice / molecular weight / Ovalbumin / Peritoneal Cavity / RNA, Messenger / Recombinant Proteins / Thioglycolates / Tumor Protein, Translationally-Controlled 1 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9834126 ● Search Scopus @ Elsevier (PMID): 9834126 (PubMed: 9834126)
111.	Shigetada Teshima, Kazuhito Rokutan, Takeshi Nikawa and Kyoichi Kishi : Guinea pig gastric mucosal cells produce abundant superoxide anion through an NADPH oxidase-like system, Gastroenterology, Vol.115, No.5, 1186-1196, 1998. (Summary) Superoxide anion (O2-) plays an important role in gastric pathophysiology. The aims of this study were to identify O2--producing activity in gastric mucosal cells and to elucidate its possible roles in inflammatory responses of the cells. The amount of O2- was measured by the reduction of cytochrome c, and O2--producing cells were visualized by nitroblue tetrazolium reaction. Cytosolic components of the phagocyte reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were detected by immunoblotting and immunocytochemical analyses with antibodies against p47-phox and p67-phox. Gastric pit cells, but not parietal cells, spontaneously released O2- at 50 nmol . mg protein-1 . h-1. NADPH or guanosine 5'-O-(3-thiotriphosphate) increased the release more than threefold, whereas diphenylene iodonium inhibited it. A reconstituted cell-free system showed that both membrane fraction and neutrophil-related cytosolic components were required for the activity. p47-phox and p67-phox were expressed in the cells. Live Helicobacter pylori organisms and their culture supernatants significantly increased the O2- release. Furthermore, H. pylori lipopolysaccharide could enhance the release more effectively than Escherichia coli lipopolysaccharide. The O2--dependent activation of nuclear factor κB occurred in these primed cells. Gastric pit cells may actively regulate inflammatory responses of gastric mucosa through a phagocyte NADPH oxidase-like activity. (Keyword) Animals / Cell-Free System / Cells, Cultured / Escherichia coli / Gastric Mucosa / Guinea Pigs / Helicobacter pylori / Lipopolysaccharides / NADPH Oxidase / NF-κB / Oxygen / Phosphoproteins / Superoxides (Link to Publication Site) ● Publication site (DOI): 10.1016/S0016-5085(98)70090-3 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9797374 ● Search Scopus @ Elsevier (PMID): 9797374 ● Search Scopus @ Elsevier (DOI): 10.1016/S0016-5085(98)70090-3 (DOI: 10.1016/S0016-5085(98)70090-3, PubMed: 9797374)
112.	Kazuhito Rokutan, Shigetada Teshima, Mami Miyoshi, Tomoko Kawai, Takeshi Nikawa and Kyoichi Kishi : Glutathione depletion inhibits oxidant-induced activation of nuclear factor-kappa B,AP-1,and c-Jun/ATF-2 in cultured guinea-pig gastric epithelial cells, Journal of Gastroenterology, Vol.33, No.5, 646-655, 1998. (Summary) The aim of this study was to reveal the role of intracellular glutathione in the oxidative stress responses of gastric epithelial cells. Metabolic radiolabeling with L-[35S]methionine and analysis of synthesized proteins by gel electrophoresis and fluorography showed that upon exposure to hydrogen peroxide (H2O2) or diamide, primary cultures of guinea-pig gastric epithelial cells rapidly induced several undefined proteins, as well as heat shock proteins. When intracellular glutathione was depleted to less than 10% of the control value by treatment with buthionine-[S,R]-sulfoximine, these inductions were completely inhibited. Gel mobility shift assay demonstrated that H2O2 and diamide rapidly activated nuclear factor-kappa B (NF-kappaB), and diamide activated activator protein (AP)-1, and c-Jun/activating transcription factor (ATF)-2, suggesting that the response may be coupled to these reduction-oxidation (redox)-sensitive transcription factors, as well as heat shock transcription factor 1. The activations of NF-kappaB, AP-1, and c-Jun/ATF-2 by the oxidants did not occur in glutathione-depleted cells. Northern blot analysis showed that glutathione depletion markedly or completely suppressed the diamide-induced expression of c-fos and c-jun mRNAs. These results suggest that intracellular glutathione redox may participate in the initiation of oxidative stress responses; thereby, it plays an important role in gastric mucosal defense. (Keyword) glutathione / gastric epithelial cells / NF-kB / AP-1 / c-Jun/ATF-2 (Link to Publication Site) ● Publication site (DOI): 10.1007/s005350050151 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9773928 ● Summary page in Scopus @ Elsevier: 2-s2.0-0031687097 (DOI: 10.1007/s005350050151, PubMed: 9773928, Elsevier: Scopus)
113.	Shigetada Kondo, Kazuhito Rokutan, Takeshi Nikawa and Kyoichi Kishi : Cultured guinea pig gastric mucosal cells produce abundant superoxide anion through an NADPH oxidase-like system., Gastroenterology, Vol.115, No.5, 1186-1196, 1998. (Keyword) superoxide / gastoric cells / host defense
114.	Takeshi Nikawa, Kazuhito Rokutan, Kayo Nanba, Kaori Tokuoka, Shigetada Teshima, Michael J Engle, David H Alpers and Kyoichi Kishi : Vitamin A Up-Regulates Expression of Bone-Type Alkaline Phosphatase in a Rat Small Intestinal Crypt Cell Line and Fetal Rat Small Intestine, Biochemical and Molecular Roles of Nutrients, Vol.128, 1869-1877, 1998. (Keyword) vitamin A / liver/bone/kidney alkaline phosphatase / IEC-6 cells / retinoid receptors / fetal rat small intestine
115.	Kazuhito Rokutan, Shigetada Teshima, Mami Miyoshi, Takeshi Nikawa and Kyoichi Kishi : Oxidant-lnduced Activation of Nuclear Factor-Kappa B in Cultured Guinea Pig Gastric Epithelial Cells, Digestive Diseases and Sciences, Vol.42, No.9, 1880-1889, 1997. (Keyword) gastric epithelial cells / oxidative stress / NF-kB / induciblc nitric oxide synthasc
116.	Tetsuya Hirakawa, Kazuhito Rokutan, Takeshi Nikawa and Kyoichi Kishi : Geranylgeranylacetone induces heat shock proteins. in cultured guinea pig gastric mucosal cells and rat gastric mucosa, Gastroenterology, Vol.111, No.2, 345-357, 1996.
117.	Shigetada Teshima, Kazuhito Rokutan, Masayuki Takahashi, Takeshi Nikawa and Kyoichi Kishi : Induction of heat shock proteins and their possible roles in macrophages during activation by macrophage colony-stimulating factor, The Biochemical Journal, Vol.315, No.Pt 2, 497-504, 1996. (Link to Publication Site) ● Publication site (DOI): 10.1042/bj3150497 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1042/bj3150497 (DOI: 10.1042/bj3150497)
118.	Arinobu Yamauchi, Fujiko Shizuka, Takashi Yamamoto, Takeshi Nikawa, Yasuhiro Kido, Kazuhito Rokutan and Kyoichi Kishi : Amino acids and glucose differentially increased extracellular 5-hydroxyindoleacetic acid of the rat brain., Journal of Nutritional Science and Vitaminology, Vol.41, No.3, 325-340, 1995. (Keyword) amino acid / serotonin / 5-HIAA / brain / glucose
119.	Takeshi Nikawa, A W. Schulz, E C. Vandenbrink, M Hanusch, P Vandersaag, W Stahl and H Sies : Efficacy of All-trans-β-Carotene, Canthaxanthin, and All-trans, 9-cis-, and 4-Oxoretinoic Acids in Inducing Differentiation of an F9 Embryonal Carcinoma RARβ-lacZ Reporter Cell Line, Archives of Biochemistry and Biophysics, Vol.316, No.2, 665-672, 1995.
120.	Shigetada Teshima, Kazuhito Rokutan, Masayuki Takahashi, Takeshi Nikawa, Yasuhiro Kido and Kyoichi Kishi : Alteration of the Respiratory Burst and Phagocytosis of Macrophages under Protein Malnutrition, Journal of Nutritional Science and Vitaminology, Vol.41, No.1, 127-137, 1995. (Keyword) protein malnutrition / macrophages / respiratory burst / phagocytosis / macrophage activation (Link to Publication Site) ● Publication site (DOI): 10.3177/jnsv.41.127 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.3177/jnsv.41.127 (DOI: 10.3177/jnsv.41.127)
121.	Takeshi Nikawa, G Schuch, G Wagner and H Sies : Interaction of ebselen with glutathione S-transferase and papain in vitro, Biochemical Pharmacology, Vol.47, No.6, 1007-1012, 1994. (Summary) The interaction of ebselen(2-phenyl-1,2-benzisoselenazol-3(2H)-one) with rat liver cytosolic glutathione S-transferases (GSTs) and the plant cysteine protease, papain, was studied as cysteine residues are important for the activity of these enzymes. The capacity of GST 1-2 and 3-4 for ebselen binding is similar (1.5 mol ebselen/mol GST isozyme), while GST 2-2 and GST 7-7 bind 0.3 and more than 2.0 mol ebselen/mol GST isozyme, respectively. Ebselen does not bind to N-ethylmaleimide-treated GST, and its binding to GST is prevented by 5 mM thiols. Ebselen irreversibly inactivates the different GST isozymes with a second order rate constant ranging from 20 to 2250 M-1 sec-1 for the different subunits. GST inhibition by ebselen is partially restored by 5 mM thiols. Ebselen binds to untreated papain and to cysteine-treated papain at a ratio of about 0.1 and 0.75 mol ebselen/mol papain, respectively. Ebselen does not bind to N-ethylmaleimide-treated papain, and its binding to papain is interfered with by added thiols. Papain is inactivated by ebselen with a second order rate constant of 1800 M-1 sec-1 in the absence of thiols. However, in the presence of GSH, 2-mercaptoethanol or sodium borohydride, ebselen exerts an activating effect on papain. The binding of ebselen by a seleno-sulfide bond to cysteine residues of GSTs and papain leads to their inactivation. (Keyword) Animals / Azoles / Ethylmaleimide / Glutathione Transferase / In Vitro Techniques / Isoenzymes / Male / Organoselenium Compounds / Papain / Rats / Rats, Wistar / Spectrophotometry, Ultraviolet / Substrate Specificity / Sulfhydryl Compounds (Link to Publication Site) ● Publication site (DOI): 10.1016/0006-2952(94)90411-1 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8147899 ● Search Scopus @ Elsevier (PMID): 8147899 ● Search Scopus @ Elsevier (DOI): 10.1016/0006-2952(94)90411-1 (DOI: 10.1016/0006-2952(94)90411-1, PubMed: 8147899)
122.	Takeshi Nikawa, G Schuch, G Wagner and H Sies : Interaction of albumin-bound ebselen with rat liver glutathione S-transferase and microsomal proteins, Biochemistry and Molecular Biology International, Vol.32, No.2, 291-298, 1994. (Summary) Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is a selenium-containing heterocyclic compound, transported bound to albumin in blood. In this report, we demonstrate the transfer of ebselen from its albumin complex to rat liver cytosolic glutathione-S-transferase (GST) and microsomal proteins, as compared to papain. Free ebselen binds to the sulfhydryl groups of proteins, such as GST and papain [Nikawa, T., Schuch, G., Wagner, G. & Sies, H. Biochem. Pharmacol. (in press)]. 2-Mercaptoethanol and N-ethylmaleimide interfere with ebselen binding to microsomal proteins, suggesting that ebselen also binds to the sulfhydryl groups of microsomal proteins. Ebselen is transferred from its albumin complex to rat liver cytosolic GST and microsomal proteins, but not to papain. These results suggest the possibility that ebselen is transferred from albumin to other proteins using their sulfhydryl groups in vivo. (Keyword) Animals / Anti-Inflammatory Agents, Non-Steroidal / Antioxidants / Azoles / Cytosol / Glutathione Transferase / Liver / Male / Microsomes, Liver / Models, Biological / Organoselenium Compounds / Papain / Protein Binding / Proteins / Rats / Rats, Wistar / Serum Albumin / Sulfhydryl Compounds (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8019434 ● Search Scopus @ Elsevier (PMID): 8019434 (PubMed: 8019434)
123.	Hisao Kakegawa, Takeshi Nikawa, Kahori Tagami, Hiroshi Kamioka, Koji Sumitani, Terushige Kawata, Marinka Drobnic-kosorok, Brigita Lenarcic, Vito Turk and Nobuhiko Katunuma : Participation of cathepsin L on bone resorption, FEBS Letters, Vol.321, No.2-3, 247-250, 1993.
124.	Takeyuki Ohshita, Takeshi Nikawa, Takae Towatari and Nobuhiko Katunuma : Effects of selective inhibition of cathepsin B and general inhibition of cysteine proteinases on lysosomal proteolysis in rat liver in vivo and in vitro, European Journal of Biochemistry, Vol.209, No.1, 2237-231, 1992.
125.	Takeshi Nikawa and 勝沼信彦 : システインプロテアーゼインヒビターによる骨粗鬆症治療の可能性, Clinical Calcium, Vol.2, No.4, 95-101, 1992.
126.	Takeshi Nikawa, Takae Towatari and Nobuhiko Katunuma : Purification and characterization of cathepsin J from rat liver, European Journal of Biochemistry, Vol.204, No.1, 381-393, 1992.
127.	Takae Towatari, Takeshi Nikawa, Mitsuo Murata, Chihiro Yokoo, Masaharu Tamai, Kazunori Hanada and Nobuhiko Katunuma : Novel epoxysuccinyl peptides A selective inhibitor of cathepsin B, in vivo, FEBS Letters, Vol.280, No.2, 311-315, 1991. (Summary) エポキシサクシニル構造を有するE-64は協力なシステインプロテアーゼインヒビターである．この側鎖を修飾することによりin vitroでシステインプロテアーゼの中でカテプシンBのみを特異的に阻害する新規E-64誘導体を開発した．
128.	Mitsuo Murata, Satsuki Miyashita, Chihiro Yokoo, Musaharu Tamai, Kazunori Hanada, Katsuo Hatayama, Takae Towatari, Takeshi Nikawa and Nobuhiko Katsunuma : Novel epoxysuccinyl peptides. Selective inhibitors of cathepsin B, in vivo, FEBS Letters, Vol.280, No.2, 307-310, 1991. (Summary) エポキシサクシニル構造を有するE-64は協力なシステインプロテアーゼインヒビターである．この側鎖を修飾することによりin vitroでシステインプロテアーゼの中でカテプシンBのみを特異的に阻害する新規E-64誘導体を開発した．
129.	Takeshi Nikawa, Takae Towatari, Yoshimasa Ike and Nobuhiko Katsunuma : Studies on the reactive site of the cystatin superfamily using recombinant cystatin A mutants, FEBS Letters, Vol.255, No.2, 309-314, 1989. (Summary) For study of the inhibition mechanism of the cystatin superfamily, cystatin A artificial mutants were obtained in which a well-conserved QVVAG region in the cystatin superfamily was changed to KVVAG or QVTAG and these mutants were then expressed in E. coli. For this, genes with these sequences were synthesized enzymatically from 11 oligodeoxynucleotides and expressed under the tac promoter gene of the E. coli plasmids. The products expressed were then purified on Sephadex G-50 and HPLC DEAE-5PW columns. The substitutions in cystatin A were confirmed by the amino acid compositions, N-terminal amino acid sequences and elution positions on ion-exchange chromatography of the products. The Ki values of these products for the cysteine proteinases, papain and cathepsins B, H and L, were determined in comparison with those of wild type recombinant cystatin A. Results showed that the cystatin A mutants had similar inhibitory activities to those of wild type recombinant cystatin A. Namely replacement of amino acids in the QVVAG sequence of cystatin A did not significantly affect the inhibitory activities on these proteinases. The results suggest that the QVVAG region is less important than the N-terminal region of cystatin for inhibitory activities on cysteine proteinases. (Keyword) Amino Acid Sequence / Animals / Base Sequence / Binding Sites / Cloning, Molecular / Cystatins / Cysteine Endopeptidases / Escherichia coli / Genes / Molecular Sequence Data / Multigene Family / Mutation / Plasmids / Promoter Regions, Genetic / Substrate Specificity (Link to Publication Site) ● Publication site (DOI): 10.1016/0014-5793(89)81112-3 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 2676604 ● Search Scopus @ Elsevier (PMID): 2676604 ● Search Scopus @ Elsevier (DOI): 10.1016/0014-5793(89)81112-3 (DOI: 10.1016/0014-5793(89)81112-3, PubMed: 2676604)

Review, Commentary:

1.	TAKATA Miho and Takeshi Nikawa : 次世代宇宙栄養学の展望, The Japanese Journal of Clinical Nutrition, Vol.142, No.1, 22-27, Jan. 2023.
2.	TAKATA Miho, Iori Sakakibara and Takeshi Nikawa : 廃用性筋萎縮の機序とその予防, 実験医学増刊号「健康寿命の鍵を握る骨格筋」, Vol.40, No.2, 100-106, Feb. 2022.
3.	Takeshi Nikawa : Japan's manned space program and space bioscience research, Journal of Clinical and Experimental Medicine, Vol.279, No.6, 669-672, Nov. 2021. (Keyword) 国際宇宙ステーション計画 (ISS計画) / 月軌道プラットフォームゲートウェイ / アルテミス計画 / コクサイウチュウステーションケイカク (ISS ケイカク) / ツキキドウプラットフォームゲートウェイ / アルテミスケイカク (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520854806260309376 (CiNii: 1520854806260309376)
4.	FUKUSHIMA Taku, Iori Sakakibara and Takeshi Nikawa : Development of functional foods effective for bedridden and weightlessness-induced muscle atrophy, Journal for the Integrated Study of Dietary Habits, Vol.32, No.2, 59-65, Sep. 2021. (Link to Publication Site) ● Publication site (DOI): 10.2740/jisdh.32.2_59 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390289920603639552 ● Search Scopus @ Elsevier (DOI): 10.2740/jisdh.32.2_59 (DOI: 10.2740/jisdh.32.2_59, CiNii: 1390289920603639552)
5.	Takeshi Nikawa, ANAYT ULLA and Iori Sakakibara : Polyphenols and Their Effects on Muscle Atrophy and Muscle Health, Molecules, Vol.26, No.16, 4887, Aug. 2021. (Summary) Skeletal muscle atrophy is the decrease in muscle mass and strength caused by reduced protein synthesis/accelerated protein degradation. Various conditions, such as denervation, disuse, aging, chronic diseases, heart disease, obstructive lung disease, diabetes, renal failure, AIDS, sepsis, cancer, and steroidal medications, can cause muscle atrophy. Mechanistically, inflammation, oxidative stress, and mitochondrial dysfunction are among the major contributors to muscle atrophy, by modulating signaling pathways that regulate muscle homeostasis. To prevent muscle catabolism and enhance muscle anabolism, several natural and synthetic compounds have been investigated. Recently, polyphenols (i.e., natural phytochemicals) have received extensive attention regarding their effect on muscle atrophy because of their potent antioxidant and anti-inflammatory properties. Numerous in vitro and in vivo studies have reported polyphenols as strongly effective bioactive molecules that attenuate muscle atrophy and enhance muscle health. This review describes polyphenols as promising bioactive molecules that impede muscle atrophy induced by various proatrophic factors. The effects of each class/subclass of polyphenolic compounds regarding protection against the muscle disorders induced by various pathological/physiological factors are summarized in tabular form and discussed. Although considerable variations in antiatrophic potencies and mechanisms were observed among structurally diverse polyphenolic compounds, they are vital factors to be considered in muscle atrophy prevention strategies. (Keyword) Animals / Anti-Inflammatory Agents / Antioxidants / Humans / Muscle, Skeletal / Muscular Atrophy / Phytochemicals / Polyphenols / Signal Transduction (Tokushima University Institutional Repository) ● Metadata: 117355 (Link to Publication Site) ● Publication site (DOI): 10.3390/molecules26164887 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34443483 ● Search Scopus @ Elsevier (PMID): 34443483 ● Search Scopus @ Elsevier (DOI): 10.3390/molecules26164887 (Tokushima University Institutional Repository: 117355, DOI: 10.3390/molecules26164887, PubMed: 34443483)
6.	Furukawa Satoshi, Chatani Masahiro, Higashitani Atsushi, Akira Higashibata, Kawano Fuminori, Takeshi Nikawa, Numaga-Tomita Takuro, Ogura Toshihiko, Sato Fuminori, Sehara-Fujisawa Atsuko, Shinohara Masahiro, Shimazu Toru, Takahash Satoru and Watanabe-Takano Haruko : Findings from recent studies by the Japan Aerospace Exploration Agency examining musculoskeletal atrophy in space and on Earth, NPJ Microgravity, Vol.7, No.1, 18, May 2021. (Summary) The musculoskeletal system provides the body with correct posture, support, stability, and mobility. It is composed of the bones, muscles, cartilage, tendons, ligaments, joints, and other connective tissues. Without effective countermeasures, prolonged spaceflight under microgravity results in marked muscle and bone atrophy. The molecular and physiological mechanisms of this atrophy under unloaded conditions are gradually being revealed through spaceflight experiments conducted by the Japan Aerospace Exploration Agency using a variety of model organisms, including both aquatic and terrestrial animals, and terrestrial experiments conducted under the Living in Space project of the Japan Ministry of Education, Culture, Sports, Science, and Technology. Increasing our knowledge in this field will lead not only to an understanding of how to prevent muscle and bone atrophy in humans undergoing long-term space voyages but also to an understanding of countermeasures against age-related locomotive syndrome in the elderly. (Tokushima University Institutional Repository) ● Metadata: 117356 (Link to Publication Site) ● Publication site (DOI): 10.1038/s41526-021-00145-9 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34039989 ● Search Scopus @ Elsevier (PMID): 34039989 ● Search Scopus @ Elsevier (DOI): 10.1038/s41526-021-00145-9 (Tokushima University Institutional Repository: 117356, DOI: 10.1038/s41526-021-00145-9, PubMed: 34039989)
7.	Takayuki Uchida, Ayako Maita and Takeshi Nikawa : 微小重力環境を利用した筋萎縮機構の研究, 実験医学増刊号, Vol.38, No.7, 82-87, Apr. 2020.
8.	Takeshi Nikawa : 機能性宇宙食の開発について, 宇宙・医学・栄養学, Vol.1, No.1, 72-77, Oct. 2019.
9.	Takayuki Uchida, Takeshi Nikawa and Reiko Nakao : Mitochondria-mediated mechanosensing mechanism in skeletal muscle, Science of the Living Body, Vol.70, No.4, 301-305, May 2019. (Keyword) ミトコンドリア / 筋肉 / IGF-1 / メカノセンシング (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1521980704885620096 (CiNii: 1521980704885620096)
10.	Takayuki Uchida and Takeshi Nikawa : 微小重力環境における筋萎縮発生メカニズムへの新展開, 月刊細胞, Vol.50, No.12, 618-621, Oct. 2018.
11.	Reiko Nakao, Takayuki Uchida and Takeshi Nikawa : サルコペニアとメカニカルストレス, 診断と治療, Vol.106, No.6, 701-704, Jun. 2018. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520573329924547328 (CiNii: 1520573329924547328)
12.	Reiko Nakao, Takeshi Nikawa and Katsutaka Oishi : The skeletal muscle circadian clock: current insights, ChronoPhysiology and Therapy, Vol.7, 47-57, Nov. 2017. (Link to Publication Site) ● Publication site (DOI): 10.2147/CPT.S116569 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.2147/CPT.S116569 (DOI: 10.2147/CPT.S116569)
13.	Ichiro Kaneko, Ken-ichi Miyamoto and Takeshi Nikawa : Vitamin D and muscle tissues, Clinical Calcium, Vol.27, No.11, 63(1571)-70(1578), Oct. 2017.
14.	Tomoki Abe, Katsuya Hirasaka and Takeshi Nikawa : Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance., World Journal of Diabetes, Vol.8, No.3, 97-103, Mar. 2017. (Summary) Aging and overnutrition cause obesity in rodents and humans. It is well-known that obesity causes various diseases by producing insulin resistance (IR). Macrophages infiltrate the adipose tissue (AT) of obese individuals and cause chronic low-level inflammation associated with IR. Macrophage infiltration is regulated by the chemokines that are released from hypertrophied adipocytes and the immune cells in AT. Saturated fatty acids are recognized by toll-like receptor 4 (TLR4) and induce inflammatory responses in AT macrophages (ATMs). The inflammatory cytokines that are released from activated ATMs promote IR in peripheral organs, such as the liver, skeletal muscle and AT. Therefore, ATM activation is a therapeutic target for IR in obesity. The ubiquitin ligase Casitas b-lineage lymphoma-b (Cbl-b) appears to potently suppress macrophage migration and activation. Cbl-b is highly expressed in leukocytes and negatively regulates signals associated with migration and activation. Cbl-b deficiency enhances ATM accumulation and IR in aging- and diet-induced obese mice. Cbl-b inhibits migration-related signals and SFA-induced TLR4 signaling in ATMs. Thus, targeting Cbl-b may be a potential therapeutic strategy to reduce the IR induced by ATM activation. In this review, we summarize the regulatory functions of Cbl-b in ATMs. (Tokushima University Institutional Repository) ● Metadata: 114501 (Link to Publication Site) ● Publication site (DOI): 10.4239/wjd.v8.i3.97 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28344752 ● Search Scopus @ Elsevier (PMID): 28344752 ● Search Scopus @ Elsevier (DOI): 10.4239/wjd.v8.i3.97 (Tokushima University Institutional Repository: 114501, DOI: 10.4239/wjd.v8.i3.97, PubMed: 28344752)
15.	Yoshihiro Sakashita, Takayuki Uchida and Takeshi Nikawa : [Impacts of physical exercise on remodeling and hypertrophy of skeletal muscle.], Clinical Calcium, Vol.27, No.1, 79-85, 2017. (Summary) The skeletal muscle has high sensitivity for the mechanical stress. Because it is enlarged by training, whereas it is easily withered by lack of exercise. When we exercise, skeletal muscle cells per se sense mechanical loading, and muscular remodeling and the muscular hypertrophy occur. It has been revealed that the intracellular signaling through PGC-1 participates in the remodeling of the skeletal muscle, while PGC-14, an isoform of PGC-1, and the dystrophin-glycoprotein complex play important roles in muscular hypertrophy. This review describes the impact of physical exercise gives on the remodeling and hypertrophy of muscle through the signaling. (Keyword) Animals / Exercise / Humans / Hypertrophy / Insulin-Like Growth Factor I / Muscle, Skeletal / Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / signal transduction (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28017949 ● Search Scopus @ Elsevier (PMID): 28017949 (PubMed: 28017949)
16.	Hikaru Kishimoto, Takayuki Uchida, Kanako Kitahata and Takeshi Nikawa : [Plasticity of skeletal muscle against unloading stress.], Clinical Calcium, Vol.27, No.3, 351-356, 2017. (Summary) Recently, muscle atrophy caused by unloading, such as spaceflight and bed rest has been becoming a social problem in Japan. However, the effective countermeasures against these disuse atrophy have not been developed. We have reviewed the mechanisms of disuse atrophy and its possible countermeasures. (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28232649 ● Search Scopus @ Elsevier (PMID): 28232649 (PubMed: 28232649)
17.	Tomoki Abe, Katsuya Hirasaka, Shohei Kohno, Arisa Ochi, Naoko Yamagishi, Ayako Ohno, Shigetada Teshima-Kondo and Takeshi Nikawa : Ubiquitin ligase Cbl-b and obesity-induced insulin resistance., Endocrine Journal, Vol.61, No.6, 529-538, Mar. 2014. (Summary) Obesity causes type 2 diabetes, atherosclerosis and cardiovascular diseases by inducing systemic insulin resistance. It is now recognized that obesity is related to chronic low-grade inflammation in adipose tissue. Specifically, activated immune cells infiltrate adipose tissue and cause inflammation. There is increasing evidence that activated macrophages accumulate in the hypertrophied adipose tissue of rodents and humans and induce systemic insulin resistance by secreting inflammatory cytokines. Accordingly, a better understanding of the molecular mechanisms underlying macrophage activation in adipose tissue will facilitate the development of new therapeutic strategies. Currently, little is known about the regulation of macrophage activation, although E3 ubiquitin ligase Casitas B-lineage lymphoma (Cbl)-b was identified recently as a novel negative regulator of macrophage activation in adipose tissue. Cbl-b, which is a suppressor of T- and B-cell activation, inhibits intracellular signal transduction by targeting some tyrosine kinases. Notably, preventing Cbl-b-mediated macrophage activation improves obesity-induced insulin resistance in mice. c-Cbl is another member of the Cbl family that is associated with insulin resistance in obesity. These reports suggest that Cbl-b and c-Cbl are potential therapeutic targets for treating obesity-induced insulin resistance. In this review, we focus on the importance of Cbl-b in macrophage activation in aging-induced and high-fat diet-induced obesity. (Link to Publication Site) ● Publication site (DOI): 10.1507/endocrj.EJ14-0048 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24614797 ● Search Scopus @ Elsevier (PMID): 24614797 ● Search Scopus @ Elsevier (DOI): 10.1507/endocrj.EJ14-0048 (DOI: 10.1507/endocrj.EJ14-0048, PubMed: 24614797)
18.	Tomoki Abe, Katsuya Hirasaka, 越智ありさ, Ayako Maita, Shigetada Kondo and Takeshi Nikawa : 免疫とインスリン抵抗性ーユビキチンリガーゼCbl-bを中心にー, 内分泌・糖尿病・代謝内科, Vol.38, No.1, 39-44, Jan. 2014. (Keyword) Cbl-b / obesity / aging / insulin resistance / macrophage
19.	aki bando, Ayako Maita and Takeshi Nikawa : 宇宙飛行と加齢による筋萎縮と栄養対策, 日本抗加齢医学会雑誌, Vol.9, No.3, 47-52, Jun. 2013.
20.	hikaru nagano, Shigetada Kondo, naoko yamagishi, chisato tomida, Ayako Maita, Katsuya Hirasaka and Takeshi Nikawa : 筋萎縮予防食開発の現状, 日本食品・機械研究会誌, Vol.33, No.3, 139-145, 2013.
21.	Chika Ikeda, Tomoki Abe, Atsuko Sakai, Katsuya Hirasaka and Takeshi Nikawa : [Space flight/bedrest immobilization and bone. Space flight and bed rest-mediated muscle atrophy]., Clinical Calcium, Vol.22, No.12, 1813-1820, Dec. 2012. (Summary) Muscle atrophy caused by unloading stress is a challenging problem for bed-rested patients or astronauts. However, countermeasures against these muscle atrophy have not been developed yet. Under unloading conditions, skeletal muscle mass is rapidly lost by the increase in protein breakdown and the decrease in protein synthesis. It has been shown that this enhancement of proteolysis in atrophying muscles results mainly from activation of the ubiquitin-proteasome proteolytic pathway. Previous our studies revealed that unloading stress led to skeletal muscle atrophy through the induction of ubiquitin ligase, Cbl-b (Casitas B-lineage lymphoma b) expression. Thus, Cbl-b inhibiters may be potent therapeutic and preventive sources against skeletal muscle atrophy caused by unloading stress. (Keyword) Bed Rest / Bone and Bones / Humans / Immobilization / Muscle, Skeletal / Muscular Atrophy / Space Flight (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23187073 ● Search Scopus @ Elsevier (PMID): 23187073 (PubMed: 23187073)
22.	Shigetada Kondo, Ochi Arisa, Shohei Kohno, Tomoki Abe, Kenro Utsunomiya, Hikaru Nagano, Takuro Suto, Chisato Tomida, Naoko Yamagishi, Katsuya Hirasaka, Ayako Maita, Yushi Okumura and Takeshi Nikawa : [Space flight/bedrest immobilization and bone. Development of inhibitors for atrophy caused by unloading stress]., Clinical Calcium, Vol.22, No.12, 1879-1885, Dec. 2012. (Summary) Muscle atrophy caused by unloading stress is a serious problem in bed rest patients or astronauts. In our previous studies, we revealed that induction and activation of ubiquitin ligase Cbl-b played an important role in skeletal muscle atrophy caused by unloading stress. Under muscle atrophy conditions, Cbl-b interacted with and degraded IRS-1 (insulin receptor substrate 1) that is a central molecule in the IGF-1 signaling pathway. In addition, we developed a Cbl-b inhibitor (Cblin) that a pentapeptide mimetic of tyrosin608-phosphorylated IRS-1, DGpYMP. This Cblin peptide inhibited Cbl-b mediated IRS-1 ubiquitination and strongly decreased the Cbl-b-mediated induction of MAFbx/atrogin-1. We are further developing Cbl-b inhibitors that are more effective than an original Cblin peptide. (Keyword) Bed Rest / Bone and Bones / Humans / Muscular Atrophy / Space Flight / Stress, Mechanical / Stress, Physiological (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23187081 ● Search Scopus @ Elsevier (PMID): 23187081 (PubMed: 23187081)
23.	Junji Terao, Takeshi Nikawa and 岡達三 : Development of the studies on physiological functions of flavonoids, Vitamins, Vol.93, 551-552, Sep. 2009.
24.	Akiko Harada, Katsuya Hirasaka, Yuushi Okumura and Takeshi Nikawa : 徳島大学栄養学発''宇宙実験''の歩みとこれから, Shikoku Acta Medica, Vol.64, No.5,6, 236-241, Dec. 2008.
25.	山田千晴, Katsuya Hirasaka, Natsuo Yasui and Takeshi Nikawa : Ubiquitin Ligase Cbl-B Mediates the Atrophy of Bone and Skeletal Muscle during Unloading(Elucidation of Mechanisum of Muscular Atrophy and Rehabilitation,43rd Annual Meeting of the Japanese Association of Rehabilitation Medicine), The Japanese Journal of Rehabilitation Medicine, Vol.44, No.3, 163-170, Mar. 2007. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520009409388112640 (CiNii: 1520009409388112640)
26.	鈴江直人, Natsuo Yasui and Takeshi Nikawa : 骨芽細胞に対するアンローディングの影響, 骨・関節・靭帯, Vol.17, No.1, 47-50, 2004.
27.	Kyoichi Kishi, Kazuhito Rokutan, Takeshi Nikawa and Shigetada Kondo : 生体におけるアミノ酸代謝, KAN TAN SUI, Vol.47, No.1, 9-16, Jul. 2003.
28.	Takeshi Nikawa, Katsuya Hirasaka, Kyoichi Kishi, 小川貴之 and Natsuo Yasui : 無重力による筋萎縮と蛋白質分解酵素, 週刊医学のあゆみ運動器科学の創生, Vol.205, No.3, 204-207, 2003.
29.	Takeshi Nikawa : 栄養と免疫機能:ビタミンAと腸管免疫, Clinical Immunology, Vol.37, No.5, May 2002.
30.	Kyoichi Kishi, Takeshi Nikawa and Kazuhito Rokutan : アミノ酸生理作用:とくにシステイン, 臨床栄養, Vol.100, No.2, 150-154, Feb. 2002.
31.	平坂勝也, 池本円, 加納美保子 and Takeshi Nikawa : 筋萎縮を改善できる新しい宇宙食の開発をめざして, 食品基材研究会, 2002.
32.	Takeshi Nikawa : サイトカイン受容体欠損マウスを用いた小腸粘膜免疫能に対するビタミンAの賦活効果の解析, 日本栄養・食料学会誌, Vol.54, No.4, 247-252, Apr. 2001.
33.	Takeshi Nikawa, Shigetada Teshima, Kazuhito Rokutan and Kyoichi Kishi : 代謝・免疫器官としての腸管:腸管局所免疫に対するビタミンAの効果, Japanese Journal of Pediatric Surgery, Vol.32, No.2, 167-173, Feb. 2000.
34.	Kyoichi Kishi, Kazuhito Rokutan and Takeshi Nikawa : ストレスと栄養:ストレスと蛋白質栄養, ストレス科学, Vol.13, No.3, 86-93, Dec. 1998.
35.	Kazuhito Rokutan, Tetsuya Hirakawa, Shigetada Teshima, Yoko Nakano, Mami Miyoshi, Tomoko Kawai, Emi Konda, Hiroko Morinaga, Takeshi Nikawa and Kyoichi Kishi : Implications of heat shock/stress proteins for medicine and disease, The Journal of Medical Investigation : JMI, Vol.44, No.3-4, 137-147, Feb. 1998. (Summary) Heat shock/stress proteins (HSPs) are crucial for maintenance of cellular homeostasis during normal cell growth and for survival during and after various cellular stresses. The HSP70 family functions as molecular chaperones and reduces stress-induced denaturation and aggregation of intracellular proteins. In addition to the chaperoning activities, HSP70 has been suggested to exert its protective action by protecting mitochondria and by interfering with the stress-induced apoptotic program. The biochemical and functional properties of HSPs observed in cultured cells may be relevant to organs and tissues in whole animals. The activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nerve system elicits the stress response in selected peripheral tissues; the HSP70 expression in the vasculature and stomach increases resistance against hemodynamic stress and stress-induced mucosal damage, respectively. Gastric mucosa pretreated with mild irritants acquires a tolerance against subsequent mucosal-damaging insults. This phenomenon is known as "adaptive cytoprotection". Transient ischemia also induces ischemic tolerance in the brain and heart, which is called "ischemic preconditioning". The heat shock response is believed to contribute to the acquisition of the tolerance. The therapeutic applications of chaperone inducers that induce HSPs without any toxic effect are also introduced. (Keyword) heat shock/stress proteins / physiologic stress / stress ulcer / ischemic tolerance / chaperone inducers (Tokushima University Institutional Repository) ● Metadata: 110658 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9597801 ● Search Scopus @ Elsevier (PMID): 9597801 (Tokushima University Institutional Repository: 110658, PubMed: 9597801)
36.	Takeshi Nikawa : 脂溶性ビタミンをめぐる新展開:新しいF9レポーター細胞に対するレチノイドとカロテノイドの分化誘導作用とその分子機構, Journal of Clinical and Experimental Medicine, Vol.178, No.2, 111-116, Jul. 1996.
37.	Takeshi Nikawa and Kazuhito Rokutan : 消化器疾患ー分子生物学的アプローチ発生・生理への分子生物学的アプローチー小腸上皮細胞の分化と分子生物学:レチノイン酸とTGF-βによる分子誘導機序を中心として, Journal of Clinical and Experimental Medicine, Vol.176, No.13, 833-836, Mar. 1996.
38.	Takeshi Nikawa and Kazuhito Rokutan : 消化管粘膜細胞と細胞増殖因子:小腸上皮細胞と増殖因子, G.I.Research, Vol.3, No.2, 50-56, Feb. 1995.
39.	Takeshi Nikawa and 勝沼信彦 : 骨吸収におけるカテプシンの役割, Biomedica, Vol.7, No.6, 657-662, Jun. 1992.
40.	Takeshi Nikawa and 勝沼信彦 : システインプロテアーゼインヒビターによる骨粗鬆症の治療の可能性, Clinical Calcium, Vol.2, No.4, 95-101, Apr. 1992.

Proceeding of International Conference:

1.	Takeshi Nikawa : Our space biomedical experiments:From Myolab to Cell Gravisencing, 12th KoSBA Symposium 2024, Jan. 2024.
2.	Akira Takahashi, Katsuyuki Miyawaki, Kazuaki Mawatari, Takeshi Nikawa, Mutsumi Aihara, Fukushima Shiho, Akizawa Shinta, Yamashita Michiyo and Koi Yumena : Development of closed-circulation soybean cultivation system applicable to extreme environments, The 3rd Japan-France International Symposium on Space Nutrition/Medicine, Kyoto, Nov. 2023.
3.	Takayuki Uchida, Miki Yukari, Katsuya Hirasaka, Sato Takahiko, Teranishi Mika, Ishihara Naotada, Kobayashi Takeshi, Higashitani Atsushi, Sokabe Masahiro and Takeshi Nikawa : The elucidation of mechanism by MFN2-mediated induction of disuse muscle atrophy, International Symposium on Mechanobiology for Human Health:8 years progress in The AMED-CREST/PRIME project on mechanobiplogy, Mar. 2023.
4.	Takeshi Nikawa, Takata Miho, Kosuke Sugiura, Takayuki Uchida, Iori Sakakibara, Madoka Uezumi and Akiyoshi Uezumi : Functional analysis of Aconitase2 in fetal skeletal muscle, International Symposium on Mechanobiology for Human Health:8 years progress in The AMED-CREST/PRIME project on mechanobiplogy, Mar. 2023.
5.	Hitoshi Takagi, Antonio Norio Nakagaito, Kawakami Nozomi, Akira Takahashi and Takeshi Nikawa : Isolation of cellulose nanofibers from soybean waste, The 9th International Forum on Advanced Technologies and The 4th Japan-Taiwan International Engineering Forum (IFAT & JTIEF 2023), 50033_1-50033_2, Taipei, Mar. 2023.
6.	Takeshi Nikawa : Food function on diseases, 第22回国際栄養学会議, Dec. 2022.
7.	Takeshi Nikawa : Anti-muscle Atrophic Effects of Dietary Cricket Proteins, International Symposium on Research and Development for Future Food and Health in Moonshot Project, Nov. 2022.
8.	Takeshi Nikawa : Relevance of Protein Nutrition on the Moon, Joint Symposium : 33rd ISTS & 10th NSAT & 14th IAA LCPM, Mar. 2022.
9.	Takeshi Nikawa : Establishing an international institute for the development of next-generation space nutrition researchers, The 3rd International Moon Village Workshop & Symposium, Kyoto, Dec. 2019.
10.	Takeshi Nikawa : Functional space foods improve the QOL in moon village, The 3rd International Moon Village Workshop & Symposium, Tokyo, Dec. 2019.
11.	(名) Anaytulla, Takayuki Uchida, Miki Yukari, Sugiura Kohsuke, Ohno Ayako, Reiko Nakao and Takeshi Nikawa : Supplementation of Morin attenuates oxidative stress and muscle wasting in mouse C2C12 skeletal myotubes treated with dexamethasone, The 7th International Conference on Food Factors(ICoFF2019)/The 12th International Conference and Exhibition on Nutraceuticals and Functional Foods (ISNFF2019), Kobe, Dec. 2019.
12.	Takayuki Uchida, Sakashita Yoshihiro, Katsuya Hirasaka, Ohno Ayako, Reiko Nakao, Akira Higashibata, Kobayashi Takeshi, Sokabe Masahiro and Takeshi Nikawa : The influence of skeletal muscle thermogenesis on the regulation of body temperature during ketogenic diet-induced hypothermia, ADVANCED BIOMEDICAL ENGINEERING AND INSTRUMENTATION SUMMIT, San Francisco, Jun. 2019.
13.	Yukiko Tomioka, Hidehiro Umehara, Shinya Watanabe, Masahito Nakataki, Masuda Rumiko, Kazuaki Mawatari, Takeshi Nikawa, Akira Takahashi, Shusuke Numata and Tetsuro Ohmori : Altered plasma metabolites related to one-carbon metabolism in schizophrenia., WFSBP Asia Pacific Regional Congress of Biological Psychiatry, Kobe, Sep. 2018.
14.	Takeshi Nikawa, Takayuki Uchida, Ayako Maita and Reiko Nakao : Molecular mechanism and nutritional approach for unloading-mediated muscle atrophy, 2018 International Conference on Functional Food for improving Sarcopenia, Cachexia and Frailty, Mar. 2018.
15.	Takeshi Nikawa : Unloading induces reactive oxygen species associated signal transduction toward atrophy in skeletal muscle cells, 3rd International Symposium on Mechanobiology, Dec. 2017.
16.	Takeshi Nikawa : Unloading induces reactive oxygen species associated signal transduction toward atrophy in skeletal muscle cells, 14th Japan-Korea Joint Seminar on Space Environment Utilization Research, Aug. 2017.
17.	Tsugita Saki, Katsuya Hirasaka, Haruna Marie, M.Mills Edward, Bando Aki, Tomoki Abe, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : Elucidation of the interaction between UCP3 and Hax-1, 11th Asian Microgravity Symposium, Oct. 2016.
18.	Takeshi Nikawa, Hashimoto Rie, Katsuya Hirasaka, Yano Chiaki, Aibara Kana, Takayuki Uchida, Tomoki Abe, Ayako Maita and Akama Kazuhito : Effects of dietary soy protein on unloading mediated muscle atrophy, 11th Asian Microgravity Symposium, Oct. 2016.
19.	Takayuki Uchida, Tomoki Abe, Ayako Maita, Reiko Nakao, Higashitani Atsushi, Kobayashi Takeshi, Sokabe Masahiro, Akira Higashibata and Takeshi Nikawa : Microgravity-induced signal transduction in skeletal muscle cells, 11th Asian Microgravity Symposium, Oct. 2016.
20.	Takeshi Nikawa : Microgravity-induced signal transduction in skeletal muscle cells, 13th Japan-Korea Joint Seminar on Space Environment Utilization Research, Oct. 2016.
21.	Ayako Maita, Tsugita Saki, Katsuya Hirasaka, Haruna Marie, Ikeda Chika, Akagi Ken-ichi, Tochio Hideto, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : Calcium-Dependent Interactive between UCP3 and Hax-1, The 27th International Conference on Msgnetic Resonance in Biological Systems, Aug. 2016.
22.	Takeshi Nikawa, Hashimoto Rie, Katsuya Hirasaka, Yano Chiaki, Aibara Kana, Ayako Maita and Akama Kazuhito : Effects of dietary soy protein on skeletal muscle volume and strength in humans with various physical activities, Molecular Mechanisms Modulating Skeletal Muscle Development and Homeostasis in Health and Disease, Jun. 2016.
23.	Uchida Takayuki and Takeshi Nikawa : Nutritional Approarch to prevent unloading-mediated muscle atrophy, 12th Japan-Korea Joint Seminar on Space Environment Utilization Research, 韓国, Oct. 2015.
24.	Tomoki Abe and Takeshi Nikawa : Capric scid up-regulates UCP3 expression without PDK4 induction in mouse C2C12 myotubes, 44th European Muscle Conference, Sep. 2015.
25.	Takagi Marina and Takeshi Nikawa : A novel functional rice against skeletal muscle atrophy caused by unloading, 44th European Muscle Conference, Sep. 2015.
26.	Takeshi Nikawa, Katsuya Hirasaka and Yuushi Okumura : Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading, 30th International Symposium on Space Technology and Science, Jul. 2015.
27.	Shigetada Kondo, Yano Chiaki, Yamagishi Naoko, Tomida Chisato, Aibara Kana, Tomoki Abe, Ayako Maita and Takeshi Nikawa : Chemopreventive effects of polyphenols on malignant phenotypes induced by chronic inhibition of VEGF in colorectal cancer cells, 12th Asian Congress of Nutrition, May 2015.
28.	Takagi Marina, Ochi Arisa, Kitahata Kanako, Kishimoto Hikaru, Nakao Reiko, Ayako Maita, Shigetada Kondo, Tomoki Abe, Hisao Nemoto and Takeshi Nikawa : N-Myristoylated ubiquitin ligase Cbl-b inhibitor prevents on glucocorticoid-induced atrophy in mouse skeletal muscle, 12th Asian Congress of Nutrition, Vol.570, No.15, 23-31, May 2015. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.abb.2015.02.006 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-84924084788 (DOI: 10.1016/j.abb.2015.02.006, Elsevier: Scopus)
29.	Tomoki Abe, Katsuya Hirasaka, Takayuki Uchida, Marina Takagi, Ayako Ohno, Shigetada Kondo and Takeshi Nikawa : Cbl-b Is a Critical Regulator of Macrophage Activation Associated With Obesity-Induced Insulin Resistance in Mice, 12th Asian Congress of Nutrition, Vol.62, No.6, 1957-1969, May 2015. (Keyword) metabolism / immunity (Link to Publication Site) ● Publication site (DOI): 10.2337/db12-0677 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23349502 ● Summary page in Scopus @ Elsevier: 2-s2.0-84878253581 (DOI: 10.2337/db12-0677, PubMed: 23349502, Elsevier: Scopus)
30.	Uchida Takayuki, Takeshi Nikawa, Tomoki Abe, Kohno Shohei, Katsuya Hirasaka, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Mills M. Edward : Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading, 12th Asian Congress of Nutrition, May 2015.
31.	Rie Mukai, Naoko Matsui, Takeshi Nikawa and Junji Terao : Dietary quercetin prevents disuse muscle atrophy of denervated mice through regulation of mitochondrial biogenesis, 12th Asian congress of Nutrition, Yokohama, May 2015.
32.	Nobuhiko Kawai, Katsuya Hirasaka, Chieko Shiota, Takeshi Nikawa and Eiji Tanaka : Effectiveness Of Myostatin Knockdown On Jaw Muscle Activity, 2014 IADR/PER Congress, Dubrovnik, Croatia., Sep. 2014.
33.	Rie Mukai, Naoko Matsui, Takeshi Nikawa and Junji Terao : Pre-intake of quercetin slow the progression of disuse muscle atrophy by mitochondrial dysfunction., XXVIIth International Conference on Polyphenols &8th Tannin Conference, Nagoya, Sep. 2014.
34.	Tomoki Abe, Utsunomiya Kenro, Yuushi Okumura, Ayako Maita, Shigetada Kondo and Takeshi Nikawa : Inhibition of myostatin activation prevents dexamethasone-induced muscle atrophy in C2C12 myotubes., The 43rd European Muscle Conference, Sep. 2014.
35.	Rie Mukai, Naoko Matsui, N Matsumoto, N.T. Dang, Takeshi Nikawa, Hisao Nemoto and Junji Terao : Anti-Oxidative Flavonoid suppresses disuse muscle atrophy in denervation mice., XXVIIth International Conference on Polyphenols &8th Tannin Conference., 2014.
36.	Takeshi Nikawa, Arisa Ochi and Tomoki Abe : Anti-muscle atrophy peptides/proteins, 10th Japan-Korea Joint Seminar on Space Environment Utilization Research, Seoul, Sep. 2013.
37.	Marie Haruna, Katsuya Hirasaka, Aki Bando, Ayako Maita, Shigetada Kondo and Takeshi Nikawa : The role of uncoupling protein 3 regulating calcium ion uptake into mitochondria during sarcopenia, 10th Japan-Korea Joint Seminar on Space Environment Utilization Research, Seoul, Sep. 2013.
38.	Tomki Abe, Shohei Kohno, Katsuya Hirasaka, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : Unloading stress disturbs muscle regeneration through perturbed recruitment and function of macrophages, The 29th International Symposium on Space Technology and Science, Nagoya, Jun. 2013.
39.	Arisa Ochi, Katsuya Hirasaka, Ayako Maita, Shigetada Kondo, Tomoyuki Kawamura, Hisao Nemoto, Rie Mukai, Junji Terao, Taesik Gwang, Inho Choi and Takeshi Nikawa : Development of anti-ubiquitination oligopeptide, Cblin:Cbl-b inhibitor that prevents unloading-induced muscle atorophy., The 29th International Symposium on Space Technology and Science, Nagoya, Jun. 2013.
40.	Takeshi Nikawa : Unloading-mediated signal transducation in skeletal muscle cells, The 22th International Rheumatology Symposium, kyoto, Apr. 2013.
41.	Rie Mukai, Takeshi Nikawa and Junji Terao : Antioxidative flavonoid quercetin suppresses disused muscle atrophy, Society for Free Radical Research International, London, Sep. 2012.
42.	Rie Mukai, Takeshi Nikawa and Junji Terao : Antioxidative flavonoid quercetin suppresses disused muscle atrophy, Free Radical Biology and Medicine, Vol.53, S87, 2012.
43.	Rie Mukai, Tomoyuki Kawamura, Hisao Nemoto, Takeshi Nikawa, Hironori Yamamoto, Eiji Takeda and Junji Terao : Flavonoid derivatives prevent disuse muscle atrophy, Internatinal Conference on Food Factors, Taipei, Nov. 2011.
44.	Katsuya Hirasaka, Edward M Mills, Kohno Shohei, Abe Tomoki, Shigetada Kondo, Ayako Maita, Yuushi Okumura and Takeshi Nikawa : Thioredoxin 2 Binding to Uncoupling Protein 3 is Processed by Inner Membrane Peptidase in the Mitochondrial Intermembrane Space and Attenuates Generation of Reactive Oxygen Species, 7th General Meeting of the International Proteolisis Society, 米国, Oct. 2011.
45.	Abe Tomoki, Katsuya Hirasaka, Kohno Shohei, Ochi Arisa, Yamashita Yui, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : Cbl-b is a Crtical Regulator of Macrophage Activation Associated with Obesity-Induced Insulin Resistance in Mice, 7th General Meeting of the International Proteolisis Society, 米国, Oct. 2011.
46.	Kohno Shohei, Shigetada Kondo, Katsuya Hirasaka, Ayako Maita, Yuushi Okumura, Rie Mukai, Junji Terao, Akira Higashibata and Takeshi Nikawa : Regulation of the Gene Expression of Cbl-b Ubiquitin Ligase in Skeletal Muscle During Unloading Conditions., 7th General Meeting of the International Proteolisis Society, 米国, Oct. 2011.
47.	Yamashita Yui, Kohno Shohei, Abe Tomoki, Ayako Maita, Shigetada Kondo, Katsuya Hirasaka, Yuushi Okumura and Takeshi Nikawa : Unloading stress disturbs muscle regeneration through perturbed recruitment and function of macrophages, 40th European Muscle Conference, ドイツ, Sep. 2011.
48.	Ochi Arisa, Nakao Reiko, Ueji Tatsuya, Katsuya Hirasaka, Ayako Maita, Shigetada Kondo, Yuushi Okumura, Nagano Keisuke, Hisao Nemoto, Akama Kazuhito and Takeshi Nikawa : Development of anti-ubiquitination oligopeptide, Cblin:Cbl-b inhibitor that prevents unloading-induced skeletal muscle atrophy., 40th European Muscle Conference, ドイツ, Sep. 2011.
49.	Takeshi Nikawa, Yama Tomorari, Kannmura Keita, Ochi Arisa, Abe Tomoki, Nakao Reiko, Kohno Shohei, Katsuya Hirasaka, Ayako Maita and Yuushi Okumura : Soy glycinin contains a functional inhibitory sequence against muscle atrophy-associated Cbl-b ubiquitin ligase, 40th European Muscle Conference, ドイツ, Sep. 2011.
50.	Tatsuya Ueji, Ayumi Shirakata, Shigetada Kondo, Keisuke Nagano, Ayako Maita, Nobuo Maita, Yuushi Okumura and Takeshi Nikawa : Crystal structure of Cbl-b TKB domain in complex with Cblin (Cbl-b inhibitor), Acta Crystallographica Section A, Vol.67, No.supplement, C304-C305, Madrid, Aug. 2011.
51.	Takeshi Nikawa, Nakao Reiko, Katsuya Hirasaka, Akira Higashibata, Inho Choi, Asashima Makoto, Edward M Mills and Yuushi Okumura : Molecular mechanism of unloading-induced muscle atrophy and development of its countermeasures, 2nd Annual Meeting of the Korean Microgravity Society,2011, Korea, May 2011.
52.	Rie Mukai, Takeshi Nikawa, Hisao Nemoto, Hironori Yamamoto, Eiji Takeda, Yoshichika Kawai and Junji Terao : Disuse muscle atrophy is suppressed by antioxidative flavonoid quercetin, International Symposium on Free Radical Research: Contribution to Medicine, Kyoto, Jan. 2011.
53.	Rie Mukai, Tomoyuki Kawamura, Yutaka Fujikura, Moemi Hayashi, Hisao Nemoto, Takeshi Nikawa, Hironori Yamamoto, Eiji Takeda and Junji Terao : Disuse muscle atrophy is prevented by flavonoids, 2010 International Chemical Congress of Pacific Basin Societies, Honolulu, Dec. 2010.
54.	Rie Murai, Tomoyuki Kawamura, Yutaka Fujikura, Moemi Hayashi, Hisao Nemoto, Takeshi Nikawa, Hironori Yamamoto, Eiji Takeda and Junji Terao : Diused muscel atrophy is prevented by flavonoids, Pachifichem 2010, Honolulu, Dec. 2010.
55.	Takeshi Nikawa : Interim report of MyoLab experiment onboard ISS and its projection to the future, 7th Korea-Japan Joint Seminar on Space Environment Utilization Research, Sep. 2010.
56.	Takeshi Nikawa : Ubiquitin ligase Cbl-b is a negative regulator for IGF-1 signaling during muscle atrophy caused by unloading, ユビキチンカンファレンス, Aug. 2010.
57.	Rie Mukai, Hitoshi Ashida, Takeshi Nikawa and Junji Terao : Nuclear accumulation of flavonol aglycone in cultured cells detected with a fluorescence microscope, 4th International Conference on Polyphenol and Health, Harrogate, United Kingdom, Dec. 2009.
58.	Yoshiko Nakae, K. Hirasaki, J. Goto, Takeshi Nikawa, Masayuki Shono, M. Yoshida and P.J. Stoward : SUBCUTANEOUS INJECTION OF EPIGALLOCATECHIN GALLATE INTO DYSTROPHIN-DEFICIENT MDX MICE AMELIORATES MUSCULAR DYSTROPHY, USA, Hawaii, Aug. 2006.
59.	Takeshi Nikawa, Madoka Ikemoto, Takako Kitano, Mihoko Kano, Shigetada Teshima, Kazuhito Rokutan, Kyoichi Kishi, Shinichi Takeda, Ikuya Nonaka, Kenneth M. Baldwin, Ryutaro Izumi and Takae Towatari : Space Shuttle flight enhances degradation of rat myosin heavy chain in association with activation of ubiquitin-proteasome pathway, 2nd iInternational Society of Proteolysis, Munich, Geramany, Oct. 2001.
60.	Takeshi Nikawa, Madoka Ikemoto, Takako Kitano, Mihoko Kano, Shigetada Teshima, Kazuhito Rokutan, Kyoichi Kishi, Shinichi Takeda, Ikuya Nonaka, Kenneth M. Baldwin, Ryutaro Izumi and Takae Towatari : Speaceflight and unweighting enhance degradation of rat myosin heavy chain in association with activation of ubiquitin-proteasome pathway and antiozidative nutrient prevents muscle protein degradation in tail-suspended rats, 17th International Congress of Nutrition, Wien, Aug. 2001.
61.	Takeshi Nikawa, Madoka Ikemoto, Chiho Watanabe, Takako Kitano, Shigetada Teshima, Kazuhito Rokutan, Kyoichi Kishi, Shinichi Takeda, Ikuya Nonaka, Kenneth M. Baldwin and Ryutaro Izumi : Tail-suspension stimulates expression of muscle proteases and cysteine supplementation prevents loss of muscle weight in tail-suspended rats, 21th Annual Gravitational Physiology Meeting, Nagoya, Apr. 2000.
62.	Takeshi Nikawa, K Tokuoka, Shigetada Teshima, Madoka Ikemoto, Takae Towatari, David H. Alpers, Kazuhito Rokutan and Kyoichi Kishi : Synergistic effects of retinoic acid and IL-1 on expression of the bone-type alkaline phosphatase and retinoid receptors in small intestinal epithelial IEC-6 cells, Annual Meeting of the American Association of the American Gastroenterological Association, Orlando, May 1999.
63.	Takeshi Nikawa, Kazuhito Rokutan, Shigetada Teshima, David H. Alpers and Kyoichi Kishi : Inflammatory cytokines are involved in retinoic acid-mediated maturation of small intestinal epithelial cells, 12th Federation of Asian and Oseanian Biochemists and Molecular Biologists, Tokushima, Oct. 1996.
64.	Takeshi Nikawa, Shigetada Teshima, David H. Alpers, Kyoichi Kishi and Kazuhito Rokutan : Involvement of inflammatory cytokines in retinoic acid-mediated maturation of small intestinal epithelial cells, Annual Meeting of the American Gastroenterological Association, San Francisco, May 1996.
65.	Takeshi Nikawa, Atsuko Sakai, M Emgle, David H. Alpers, Kazuhito Rokutan and Kyoichi Kishi : Stimulatory action of retinoic acid on differentiation of rat small intestinal cells, Annual Meeting of the American Gastroenterological Association, San Diego, May 1995.
66.	Takeshi Nikawa, A W. Schulz, E C. Vandenbrink, M Hanusch, P Vandersaag, W Stahl and H Sies : Efficacy of all-trans-β-carotene, canthaxanthin, and all-trans, 9-cis-, and 4-oxoretinoic acids in Inducing differentiation of an F9 embryonal carcinoma RARβ-lacZ reporter cell line, 2nd International Congress of Vitammins and Biofactors, San Diego, Feb. 1995.
67.	Takeshi Nikawa, G Schuch, G Wagner and H Sies : Interaction of ebselen with glutathione S-transferase and papain in vitro, Annual Autumu Meeting of German Biochemical Society, Dusseldorf, Germany, Sep. 1993.
68.	Takeshi Nikawa : Ebselen : its pharmaceutical role as an antioxidative agent, ドイツフライブルク大学招待講演, Freiburg, Germany, Jul. 1993.
69.	Takeshi Nikawa, Takae Towatari and Nobuhiko Katunuma : A novel lysosomal cysteine protease:low sensitivity for E-64, 8th International Congress on Proteolysis,, Munich, Germany, Nov. 1990.

Proceeding of Domestic Conference:

1.	Takeshi Nikawa : 宇宙栄養学∼有人宇宙活動を支える機能性宇宙食の開発∼, 第94回日本衛生学会学術集会, Mar. 2024.
2.	Takeshi Nikawa : 抗筋萎縮活性を有する機能性宇宙食の開発, 第22回日本栄養改善学会近畿支部会学術総会, Dec. 2023.
3.	YUKA Hasegawa, Madoka Uezumi, 林晋一郎, 野口悟, 西野一三, 黒澤珠希, Takeshi Nikawa and Akiyoshi Uezumi : 間葉系前駆細胞の不均一性が支える筋健全性維持機構の解明, 第46回日本分子生物学会年会, Dec. 2023.
4.	Takeshi Nikawa : 代替食品・大豆たんぱく質の抗筋萎縮効果, 第45回日本臨床栄養学会・第44回日本臨床栄養協会第21回大連合大会, Nov. 2023.
5.	Hitoshi Takagi, Antonio Norio Nakagaito, Kawakami Nozomi, Akira Takahashi and Takeshi Nikawa : Extraction and evaluation of cellulose nanofibers from soybean waste, 29th Green Composite Working Group Meeting and Research Presentation Abstracts, 4, Oct. 2023.
6.	AIZAWA Shinta, KOI Yumena, MICHIYO Yamashita, 白石志帆, Katsuyuki Miyawaki, Mutsumi Aihara, Takeshi Nikawa, Takashi Uebanso, Kazuaki Mawatari and Akira Takahashi : 極地環境での大豆栽培方法の確立, 第56回日本栄養·食糧学会中国·四国支部大会, Oct. 2023.
7.	Chinami Itoh, MINORI Suzuki, HIROKI Matsuki, ANAYT ULLA, Takayuki Uchida, 中森俊宏, 松井利郎 and Takeshi Nikawa : 大豆タンパク質の抗筋萎縮活性, 第56回日本栄養・食糧学会中国・四国支部大会, Oct. 2023.
8.	Erika Yamano, KISHIDA Kohta, TAKATA Miho, Kosuke Sugiura, 柳原裕太, 今井祐記, 田中かおり, 高橋智, Iori Sakakibara, Madoka Uezumi, Akiyoshi Uezumi and Takeshi Nikawa : 成体骨格筋におけるAconitase2の機能解明, 第56回日本栄養・食糧学会中国・四国支部大会, Oct. 2023.
9.	Haruka Tsuda, Kanako Kitahata, Takayuki Uchida, 橋爪藤子, Akira Higashibata, Junsoo Park, Inho Choi and Takeshi Nikawa : 3D-clinorotation によるラットL6 筋管萎縮に対するC14-Cblin とセラストロールの同時投与による相加効果, 日本宇宙生物科学会第37回大会, Sep. 2023.
10.	Takeshi Nikawa : 無重力による筋萎縮のメカニズムとその栄養学的治療法, 第59回日本医学放射線学会秋季臨床大会, Sep. 2023.
11.	ANAYT ULLA, Mizanur Md Rahman, Takayuki Uchida, Hiroyuki Kayaki, Yosuke Nishitani, Susumu Yoshino, Hiroshige Kuwahara and Takeshi Nikawa : 3-(4-hydroxy-3-methoxyphenyl) propionic acid attenuates dexamethasone-induced muscle atrophy by suppressing Atrogin-1 and MuRF-1, 日本食品科学工学会第70回記念大会, Aug. 2023.
12.	Takeshi Nikawa : ポリフェノールと筋萎縮抑制について, 日本食品科学工学会第70回記念大会, Aug. 2023.
13.	YUKA Hasegawa, Madoka Uezumi, 林晉一郎, 野口悟, 西野一三, 黒澤珠希, Takeshi Nikawa and Akiyoshi Uezumi : 間葉系前駆細胞の不均一性が支える筋健全性維持メカニズムの解明, 合同学術集会第9回日本筋学会学術集会第10回筋ジストロフィー医療研究会, Aug. 2023.
14.	Takeshi Nikawa, KISHIDA Kohta, TAKATA Miho, Iori Sakakibara, 今井祐記, Madoka Uezumi and Akiyoshi Uezumi : 筋特異的ノックアウトマウスを用いたミトコンドリアアコニターゼの機能解析, 合同学術集会第9回日本筋学会学術集会第10回筋ジストロフィー医療研究会, Aug. 2023.
15.	Takeshi Nikawa : 宇宙実験から得た新発見!大豆たんぱく質の抗筋萎縮活性と未来への期待, 日本外科代謝栄養学会第60回学術集会, Jul. 2023.
16.	Takeshi Nikawa : 寝たきりや無重力による筋萎縮と酸化ストレス, 第76回日本酸化ストレス学会学術集会, May 2023.
17.	YUKA Hasegawa, Madoka Uezumi, 黒澤珠希, Takeshi Nikawa and Akiyoshi Uezumi : 間葉系前駆細胞の不均一性が支える筋健全性維持機構の解明, 第77回日本栄養・食糧学会大会, May 2023.
18.	Chinami Itoh, HIROKI Matsuki, MINORI Suzuki, KONO Madoka, ANAYT ULLA, Takayuki Uchida, 石黒貴寛 and Takeshi Nikawa : 高野豆腐タンパク質の抗筋萎縮活性の解析, 第77回日本栄養・食糧学会大会, May 2023.
19.	Takayuki Uchida, ARAKAKI Tsubasa, Haruka Tsuda, TANIGUCHI Runa, 山本綾乃 and Takeshi Nikawa : 筋ミトコンドリアタンパク質Mitofusin2(Mfn2)による脂質代謝制御機構の解明, 第77回日本栄養・食糧学会大会, May 2023.
20.	Haruka Tsuda, Takayuki Uchida, Izumi Kawabata, ANAYT ULLA, TANIGUCHI Runa and Takeshi Nikawa : 筋肉へのピセアタンノール作用の検討, 第77回日本栄養・食糧学会大会, May 2023.
21.	HIROKI Matsuki, MINORI Suzuki, KONO Madoka, ANAYT ULLA, Kazuaki Mawatari, Akira Takahashi, Katsuyuki Miyawaki, Takahito Watanabe, Taro Mito, Takayoshi Kuriki and Takeshi Nikawa : コオロギの抗筋萎縮作用について, 第77回日本栄養・食糧学会大会, May 2023.
22.	Erika Yamano, Chinami Itoh, HIROKI Matsuki, KONO Madoka, ANAYT ULLA, Takayuki Uchida, Takashi Uebanso, Hitoshi Takagi and Takeshi Nikawa : セルロースナノファイバーの栄養学的機能性の検討, 第77回日本栄養・食糧学会大会, May 2023.
23.	Takeshi Nikawa : 有人宇宙活動を支える機能性宇宙食の開発, 第77回日本栄養・食糧学会大会, May 2023.
24.	井上慎太郎, Takahito Watanabe, HAMAGUCHI Taiki, Yoshiyasu Ishimaru, Katsuyuki Miyawaki, Takeshi Nikawa, Akira Takahashi, Sumihare Noji and Taro Mito : コオロギをモデルとした体色パターン制御の分子メカニズムの解析, 第67回日本応用動物昆虫学会, Mar. 2023.
25.	HAMAGUCHI Taiki, 井上慎太郎, Katsuyuki Miyawaki, Akira Takahashi, Takeshi Nikawa, Yoshiyasu Ishimaru, Sumihare Noji, Takahito Watanabe and Taro Mito : フタホシコオロギにおける色素合成に関わる遺伝子の機能解析, 第45回日本分子生物学会, Dec. 2022.
26.	YUKA Hasegawa, Madoka Uezumi, 黒澤珠希, Takeshi Nikawa and Akiyoshi Uezumi : 間葉系前駆細胞の不均一性が支える筋健全性維持機構の解明, 第45回日本分子生物学会年会, Dec. 2022.
27.	Honoka Kamakura, Madoka Uezumi, 黒澤珠希, Tomoya Fukawa, Takeshi Nikawa and Akiyoshi Uezumi : ヒト筋幹細胞を用いた筋肥大作用を有する天然由来生理活性生物の同定, 第45回日本分子生物学会年会, Dec. 2022.
28.	TANAKA Yukako, KOMATSU Rina, HIRATA Shuya, Tomoya Fukawa and Takeshi Nikawa : がん由来エクソソーム内 micro RNA によるミトコンドリア呼吸鎖複合体制御と筋萎縮発症機序の解明, 第55回日本栄養・食糧学会中国・四国支部大会, Oct. 2022.
29.	Haruka Tsuda, Takayuki Uchida, Izumi Kawabata, (名) ANAYTULLA, TANIGUCHI Runa, 内田裕子, 森貞夫, 守田稔 and Takeshi Nikawa : C2C12 筋管細胞へのピセアタンノールの影響, 第55回日本栄養・食糧学会中国・四国支部大会, Oct. 2022.
30.	TANIGUCHI Runa, Kanako Kitahata, Takayuki Uchida, Ayano Katoh, KISHIDA Kohta, TANAKA Yukako, Junsoo Park, Choi Inho and Takeshi Nikawa : 3D-clinorotation によるラット L6 筋管萎縮に対する C14-Cblin とセラストロールの同時投与による相加効果, 第55回日本栄養・食糧学会中国・四国支部大会, Oct. 2022.
31.	KISHIDA Kohta, TAKATA Miho, Kosuke Sugiura, Takayuki Uchida, Iori Sakakibara, Madoka Uezumi, Akiyoshi Uezumi and Takeshi Nikawa : Aconitase2, 第55回日本栄養・食糧学会中国・四国支部大会, Oct. 2022.
32.	Takeshi Nikawa : 有人宇宙活動を支える機能性宇宙食の開発, 日本宇宙生物科学会第36回大会, Sep. 2022.
33.	TAKATA Miho, KISHIDA Kohta, Kosuke Sugiura, Takayuki Uchida, 榊原伊織, Madoka Uezumi, Akiyoshi Uezumi and Takeshi Nikawa : 胎生期骨格筋における Aconitase2 の機能解析, 日本宇宙生物科学会第36回大会, Sep. 2022.
34.	Takeshi Nikawa : (無)重力感知の分子メカニズムとその制御による筋萎縮と骨粗鬆症の抑制, 第35回日本臨床整形外科学会学術集会, Jul. 2022.
35.	Takeshi Nikawa : 宇宙飛行と加齢による筋萎縮と栄養対策, 第22回日本抗加齢医学会総会, Jun. 2022.
36.	TAKATA Miho, Iori Sakakibara, KISHIDA Kohta, FUKUSHIMA Taku, ARAKAKI Tsubasa, Takayuki Uchida, Tomoya Fukawa and Takeshi Nikawa : 骨格筋におけるAconitase2の機能解明, 第76回日本栄養・食糧学会大会, Jun. 2022.
37.	Minori Yamasaki, HIROKI Matsuki, NAKANO Wataru, Kosuke Sugiura, Tomoya Fukawa, Takayuki Uchida, Iori Sakakibara and Takeshi Nikawa : 廃用性筋萎縮におけるアコニターゼ活性の低下とその栄養学的保護, 第76回日本栄養・食糧学会大会, Jun. 2022.
38.	HIROKI Matsuki, Minori Yamasaki, KONO Madoka, NAKANO Wataru, (名) ANAYTULLA, Akira Takahashi, Katsuyuki Miyawaki, Takahito Watanabe, Taro Mito, Takayoshi Kuriki and Takeshi Nikawa : コオロギの抗筋萎縮作用について, 第76回日本栄養・食糧学会大会, Jun. 2022.
39.	ARAKAKI Tsubasa, TANIGUCHI Runa, Erika Aoki, Ayaka Satoh, TAKATA Miho, Takayuki Uchida and Takeshi Nikawa : 高脂肪負荷食によるMfn2と骨格筋エネルギー代謝の関連解明, 第76回日本栄養・食糧学会大会, Jun. 2022.
40.	NAKANO Wataru, Kosuke Sugiura, Takayuki Uchida, Iori Sakakibara, Koichi Sairyo and Takeshi Nikawa : 廃用性萎縮筋におけるアコニターゼ活性とその保護, 第 54 回日本栄養•食糧学会中国•四国支部大会第7 回日本栄養改善学会四国支部学術総会合同大会, Oct. 2021.
41.	Takeshi Nikawa : 安全・安心な長期宇宙滞在を実現するための「食」戦略, 日本宇宙生物科学会第35回大会, Oct. 2021.
42.	Takeshi Nikawa : 安全・安心の長期宇宙滞在を支援する機能性宇宙食の開発, 日本宇宙生物科学会第35回大会, Sep. 2021.
43.	ADACHI Yuichiroh, Masashi Masuda, Iori Sakakibara, Takayuki Uchida, Hirokazu Ohminami, Hisami Okumura, Takeshi Nikawa and Yutaka Taketani : all trans レチノイン酸は小胞体ストレス応答関連因子 GADD34 の転写・転写後制御を介して筋繊維タイプ変化を引き起こす, 第 62 回日本生化学会中国・四国支部例会, Sep. 2021.
44.	KONO Madoka, Takayuki Uchida, Akane Ohishi, HIRAYAMA Kako, TAKEMURA Yuma, Shoichiro Takao, Yuki Kanazawa, Yuki Matsumoto, Masafumi Harada, Iori Sakakibara, 鈴木利雄 and Takeshi Nikawa : 蒸し大豆食品の継続摂取が運動不足の健常人の筋量や筋力に及ぼす影響, 第75回日本栄養・食糧学会大会, Jul. 2021.
45.	TANIGUCHI Runa, Izumi Kawabata, Takayuki Uchida, (名) ANAYTULLA, Iori Sakakibara and Takeshi Nikawa : パッションフルーツ種子由来成分ピセアタンノールはデキサメタゾン誘導性筋萎縮を抑制する, 第75回日本栄養・食糧学会大会, Jul. 2021.
46.	ADACHI Yuichiroh, Masashi Masuda, Iori Sakakibara, Takayuki Uchida, SASAKI Kohei, NOBE Yutaro, Hirokazu Ohminami, Kohta Ohnishi, Hisami Okumura, Hironori Yamamoto, Takeshi Nikawa and Yutaka Taketani : all trans レチノイン酸は小胞体ストレス応答関連因子 GADD34 の発現制御を介して筋繊維タイプ変化を誘導する, 第 75 回日本栄養・食糧学会大会, Jul. 2021.
47.	Takeshi Nikawa : 有人宇宙活動を支える機能性宇宙食材の食料自給システムの確立, 日本地球惑星科学連合2021年大会, Jun. 2021.
48.	Takeshi Nikawa : 寝たきりや無重力による筋萎縮に有効な機能性食材の開発, 第62回日本食生活学会, May 2021.
49.	Takeshi Nikawa : 無重力による筋萎縮の分子メカニズムとその栄養学的予防法, 第64回日本糖尿病学会年次学術集会プログラム, May 2021.
50.	Kosuke Sugiura, Takeshi Nikawa and Koichi Sairyo : 骨格筋の廃用による活性酸素種(ROS)の発生がアコニターゼ活性に与える影響と筋萎縮における役割の解明, 第136回中部整形外科災害外科学会・学術集会, Apr. 2021.
51.	Takeshi Nikawa : Microgravity and aging-mediated muscle atrophy and its nutritional regeneration, 第20回日本再生医療学会総会, Mar. 2021.
52.	Iori Sakakibara, Kosuke Sugiura, Takayuki Uchida, Higashitani Atsushi, Kobayashi Takeshi, Sokabe Masahiro and Takeshi Nikawa : Mechano-signals regulate mitochondria-associated membrane, 第43回日本分子生物学会年会, Dec. 2020.
53.	Reiko Nakao, Takeshi Nikawa and Katsutaka Oishi : Skeletal muscle thermogenesis during ketogenic diet-induced hypothermia, 第43回日本分子生物学会年会, Dec. 2020.
54.	Ayano Katoh, Takayuki Uchida, Iori Sakakibara, 池田泰隆, 濱田広一郎 and Takeshi Nikawa : 細胞内エネルギー代謝が筋細胞に与える影響, 第53回日本栄養食糧学会中国・四国支部大会, Oct. 2020.
55.	NAKANO Wataru, 三木裕可里, Kosuke Sugiura, Iori Sakakibara, Takayuki Uchida and Takeshi Nikawa : ミトコンドリア小胞体接触領域 (MAM) を介した筋量調節メカニズムの解明, 第53回日本栄養食糧学会中国・四国支部大会, Oct. 2020.
56.	Kosuke Sugiura, Takayuki Uchida, Koichi Sairyo and Takeshi Nikawa : (ROS)Mitochondrial Aconitase, 35, Oct. 2020.
57.	Takeshi Nikawa : 特殊環境の筋蛋白質分解とその栄養学的制御法, 第48回日本歯科麻酔学会総会・学術集会, Oct. 2020.
58.	Takeshi Nikawa : 無重力や寝たきりによる筋萎縮のメカニズムとその栄養学的アプローチ, 「食」と「健康」ラボ研究会第5回シンポジウム, Aug. 2020.
59.	Takeshi Nikawa : 宇宙実験から得られた無重力による筋萎縮の新たな知見, 第40回日本骨形態計測学会, Jun. 2020.
60.	Takeshi Nikawa : Mechanism of unloading-mediated muscle atrophy focused on sensing mechanism of unloading stress, 第59回日本生体医工学会大会, May 2020.
61.	Koichi Sairyo, Kosuke Sugiura, Takayuki Uchida and Takeshi Nikawa : ミトコンドリア-小胞体接触領域(MAM)は廃用性筋委縮を制御する(一般演題基礎:筋・腱・滑膜 ), 第93回日本整形外科学会学術総会【WEB】, May 2020.
62.	Takayuki Uchida, Yukari Miki, Kosuke Sugiura, Ayako Maita, Reiko Nakao, 平坂勝也, 東谷篤志, 小林剛, 曽我部正博 and Takeshi Nikawa : 筋肉におけるミトコンドリアタンパク質Mfn2の役割, 第74回日本栄養・食糧学会大会, May 2020.
63.	Taiju Fujioka, Takayuki Uchida, Kosuke Sugiura, 小林剛, 東谷篤志, 曽我部正博 and Takeshi Nikawa : Unloadingによる筋萎縮におけるCa2+-ROSシグナルの変化, 第74回日本栄養・食糧学会大会, May 2020.
64.	Ayano Katoh, Takayuki Uchida, Kosuke Sugiura, 池田泰隆, 濱田広一郎 and Takeshi Nikawa : 細胞内エネルギー代謝経路が筋繊維タイプに与える影響, 第74回日本栄養・食糧学会大会, May 2020.
65.	Izumi Kawabata, Takayuki Uchida, Ayano Katoh, Ulla Anayt, 内田裕子, 森貞夫, 森田稔 and Takeshi Nikawa : ピセアタンノールの筋萎縮抑制効果の検討, 第74回日本栄養・食糧学会大会, May 2020.
66.	佐藤友紀, Reiko Nakao, 山本彩音 and Takeshi Nikawa : 大豆タンパク質の摂取はケトジェニックダイエットによる体温の日内リズム乱れを改善する, 第74回日本栄養・食糧学会大会, May 2020.
67.	Takeshi Nikawa : 機能性食材による筋萎縮の予防, 第74回日本栄養・食糧学会大会, May 2020.
68.	Takeshi Nikawa : 寝たきりや無重力による筋萎縮の分子メカニズムとその栄養学的予防法の開発, 第6回京都リハビリテーション医学会学術集会, Feb. 2020.
69.	Yuuki Niida, Masashi Masuda, Aika Yoshizawa, Yuichiroh Adachi, Kohta Ohnishi, Hirokazu Ohminami, Takayuki Uchida, Hisami Okumura, Takeshi Nikawa, Hironori Yamamoto and Yutaka Taketani : 慢性腎臓病による骨格筋の脂肪酸代謝異常を介した脂肪毒性(Liptoxicity)は筋委縮(サルコペニア) を惹起する, 第23回日本病態栄養学会年次集会, Jan. 2020.
70.	Takeshi Nikawa : 月・火星の有人探査に向けて日本宇宙生物科学会の果たすべき役割, 第34回宇宙環境利用シンポジウム, Jan. 2020.
71.	Katsuya Hirasaka, M.Mills Edward, Takayuki Uchida, Ohno Ayako and Takeshi Nikawa : New aspect of mitochondrial uncoupling protein(UCP):Identification of UCP3 interacting proteins, 第42回日本分子生物学会年会, Dec. 2019.
72.	Takeshi Nikawa, Akira Takahashi and Katsuyuki Miyawaki : 機能性宇宙食, 第63回宇宙科学技術連合講演会, Nov. 2019.
73.	Yuki Mori, Masashi Masuda, Risa Yoshida, Saki Aoyagi, Kohta Ohnishi, Hirokazu Ohminami, Hisami Okumura, Takeshi Nikawa, 濱田広一郎 and Yutaka Taketani : レチノイン酸によるリポファジーを介した脂肪分解への影響, 第52回日本栄養・食糧学会中国•四国支部大会, Oct. 2019.
74.	Izumi Kawabata, Takayuki Uchida, Ayano Katoh, (名) Anaytulla, 内田裕子, 森貞夫, 森田稔 and Takeshi Nikawa : ピセアタンノールの筋萎縮抑制効果の検討, 第52回日本栄養・食慮学会中国・四国支部大会, Oct. 2019.
75.	Takeshi Nikawa : Unloadingストレスの感知とオルガネラ連関, 第34回日本整形外科学会基礎学術集会, Oct. 2019.
76.	Takeshi Nikawa : 機能性宇宙食の開発, 第66回日本栄養改善学会学術総会, Sep. 2019.
77.	Yuuki Niida, Masashi Masuda, Aika Yoshizawa, Yuichiroh Adachi, Kohta Ohnishi, Hirokazu Ohminami, Takayuki Uchida, Hisami Okumura, Takeshi Nikawa, Hironori Yamamoto and Yutaka Taketani : 慢性腎臓病モデルラットの骨格筋における脂肪酸代謝異常が及ぼす筋萎縮への影響, 第66回日本栄養改善学会学術集会, Sep. 2019.
78.	Takeshi Nikawa : 無重力や寝たきりによる筋萎縮に有効な機能性宇宙食の開発, 日本食品科学工業会第66回大会, Aug. 2019.
79.	Takeshi Nikawa : 廃用性筋萎縮の分子メカニズムとその栄養学的予防法, 第5回Neo VitamineD Workshop学術集会, Aug. 2019.
80.	Kohsuke Sugiura, Takayuki Uchida, Ayako Maita, Reiko Nakao, Katsuya Hirasaka, 東谷篤志, Akira Higashibata, 小林剛, 曽我部正博, Koichi Sairyo and Takeshi Nikawa : 廃用性筋萎縮におけるミトコンドリア形態変化及び酸化ストレス発生による影響, 日本筋学会第5回学術集会, Aug. 2019.
81.	Yuichiroh Adachi, Masashi Masuda, Yuuki Niida, Kohta Ohnishi, Takayuki Uchida, Hisami Okumura, Hironori Yamamoto, Takeshi Nikawa and Yutaka Taketani : レチノイン酸による小胞体ストレス感受性の影響, 日本ビタミン学会第71回大会, Jun. 2019.
82.	Yukari Miki, Akio Komatsu, Takayuki Uchida, Reiko Nakao, Ayako Maita, 曽我部正博 and Takeshi Nikawa : 廃用性筋萎縮進展におけるミトコンドリアタンパク質Mfn2の役割, 第73回日本栄養・食糧学会大会, May 2019.
83.	Takayuki Uchida, Yukari Miki, Yoshihiro Sakashita, 真板綾子, Reiko Nakao, Katsuya Hirasaka, 東谷篤志, Akira Higashibata, 小林剛, 曽我部正博 and Takeshi Nikawa : ミトコンドリアを介した無重力ストレス感知機構の解明, 第73回日本栄養・食糧学会大会, May 2019.
84.	Takeshi Nikawa : サルコペニアの発症機序と栄養学的治療, 第73回日本栄養・食糧学会大会, May 2019.
85.	Takeshi Nikawa : 無重力によるミトコンドリア機能異常と筋萎縮, 第92回日本整形外科学会学術総会, May 2019.
86.	Reiko Nakao, Katsuyuki Miyawaki, Yoshihiro Deguchi, Akira Takahashi and Takeshi Nikawa : 宇宙栄養・食糧関連技術の開発とGatewayへの期待, 国際宇宙探査ワークショップ(その2), Mar. 2019.
87.	Takayuki Uchida, Ayako Maita, Reiko Nakao and Takeshi Nikawa : 宇宙医学から健康長寿へ, 第221回徳島医学会学術集会, Feb. 2019. (Keyword) muscle atrophy / mitochondria
88.	Takeshi Nikawa, Takayuki Uchida, Reiko Nakao, Katsuya Hirasaka, Nobuo Maita, 東谷篤志, 小林剛, 石原直忠 and 曽我部正博 : Unloadingストレスに対する筋細胞の初期応答:酸化ストレスの重要性, 第41回日本分子生物学会年会, Nov. 2018.
89.	足立雄一郎, Masashi Masuda, 新井田裕樹, Kohta Ohnishi, Takayuki Uchida, Hisami Okumura, Takeshi Nikawa and Yutaka Taketani : 小胞体ストレス誘導下におけるレチノイン酸の影響, 第51回日本栄養・食糧学会中国・四国支部大会, Nov. 2018.
90.	Yuki Satoh, Reiko Nakao, 赤間一仁 and Takeshi Nikawa : Cbl-b阻害ペプチド高含有米の除神経性筋萎縮改善作用の評価, 第51回日本栄養・食糧学会中国・四国支部大会, Nov. 2018.
91.	Yukari Miki, Takayuki Uchida, Yuki Kimori, Yoshihiro Sakashita, Akio Komatsu, Ayako Maita, Reiko Nakao, Miyu Uchida, Taiju Fujioka, 小林剛, 東谷篤志, 石原直忠, 東端晃, 石岡憲昭, 武田伸一, 曽我部正博 and Takeshi Nikawa : ユビキチンリガーゼCbl-bは無重力ストレス誘導性の酸化ストレスにより増大する, 第51回日本栄養・食糧学会中国・四国支部大会, Nov. 2018.
92.	Takeshi Nikawa : 無重力による筋萎縮とその栄養学的予防法, 日本宇宙生物科学会第32回大会, Sep. 2018.
93.	Yukari Miki, Takayuki Uchida, Yuki Kimori, Yoshihiro Sakashita, Akio Komatsu, Ayako Maita, Reiko Nakao, Miyu Uchida, Taiju Fujioka, 小林剛, 東谷篤志, 石原直忠, 東端晃, 石岡憲昭, 武田伸一, 曽我部正博 and Takeshi Nikawa : 酸化ストレスはラットL6細胞におけるユビキチンリガーゼCbl-bの発現を増大する, 日本宇宙生物科学会第32回大会, Sep. 2018.
94.	Takeshi Nikawa : 筋細胞における無重力ストレスのシグナル・トランスダクション, 日本植物学会第82回大会, Sep. 2018.
95.	吉田里沙, Masashi Masuda, 森優樹, 新井田裕樹, 足立雄一郎, Kohta Ohnishi, Yoshichika Kawai, Takeshi Nikawa, 山本浩範 and Yutaka Taketani : スルフォラファンのリポファジーを介した脂肪分解効果, Food Congress 2018, Sep. 2018.
96.	Akio Komatsu, Takayuki Uchida, Kanako Kitahata, Ayako Maita, Reiko Nakao, 瀬川圭 and Takeshi Nikawa : 廃用性筋萎縮を抑制するユビキチンリガーゼCbl-bの低分子阻害剤の開発, 日本筋学会第4回学術集会, Aug. 2018.
97.	Ayako Maita, Nobuo Maita, Yuushi Okumura, Takayuki Uchida, Reiko Nakao, Koji Kishimoto and Takeshi Nikawa : 高病原性インフルエンザ感染に関わる宿主酵素MSPLと阻害剤との複合体構造., 病態プロテアーゼ学会, Aug. 2018.
98.	Takeshi Nikawa : 宇宙実験から得た抗筋萎縮栄養法, 第6回日本腎栄養代謝研究会学術集会・総会, Jul. 2018.
99.	Yuuki Niida, Masashi Masuda, Aika Yoshizawa, Yuichiroh Adachi, Takayuki Uchida, Kohta Ohnishi, Yoshichika Kawai, Takeshi Nikawa, Hironori Yamamoto and Yutaka Taketani : 慢性腎臓病に伴う骨格筋の飽和脂肪酸蓄積はオートファジー不全を介して筋萎縮を誘発する, 日本ビタミン学会第70回大会(高槻現代劇場), Jun. 2018.
100.	Koji Kishimoto, Takashi Hraguchi, Kenji Shimizu, Ide Munenori, Miyashita Tomoharu, Ohno Ayako, Takeshi Nikawa and Izumi Tkashi : An oxidazed lipids-membrane receptor, human G2A regulates epithelial-mesenchymal transition-like proces of glioma cells., 第59回日本生化学会中国四国支部例会(口頭), 85, May 2018. (Keyword) G2A / 酸化脂質
101.	Miyuki Ninomiya, Yuki Kimori, Akio Komatsu, Ayaka Tetsuno, Yukari Miki, Kanako Kitahata, Takayuki Uchida, Ayako Maita, Reiko Nakao, 松井利郎, 赤間一仁 and Takeshi Nikawa : 廃用性筋萎縮を防ぐ高機能米の開発, 第72回日本栄養・食糧学会大会, May 2018.
102.	Takeshi Nikawa : 癌カヘキシアによる筋萎縮に有効な食材の開発, 第72回日本栄養・食糧学会大会, May 2018.
103.	Takeshi Nikawa : 長期滞在する宇宙飛行士(宇宙人)の主食開発, 第72回日本栄養・食糧学会大会, May 2018.
104.	Risa Yoshida, Yuuki Niida, Yuichiroh Adachi, 酒井晶子, Hisami Okumura, Kohta Ohnishi, Takayuki Uchida, Yoshichika Kawai, Hironori Yamamoto, Takeshi Nikawa, Yutaka Taketani and Masashi Masuda : スルフォラファンのリポファジーを介した脂肪分解効果, 第72回日本栄養・食糧学会大会(岡山県立大学), May 2018.
105.	Yuki Kimori, Miyuki Ninomiya, Yukari Miki, Akio Komatsu, Ayaka Tetsuno, Takayuki Uchida, Reiko Nakao, Ayako Maita, 近藤茂忠, 曽我部正博 and Takeshi Nikawa : 無重力環境におけるミトコンドリアタンパク質Mitofusin2(Mfn2)の役割, 第72回日本栄養・食糧学会大会, May 2018.
106.	Takayuki Uchida, Yuki Kimori, Yoshihiro Sakashita, Ayako Maita, Reiko Nakao, 平坂勝也, 東谷篤志, 東端晃, 小林剛, 曽我部正博, 武田伸一 and Takeshi Nikawa : 無重力による廃用性筋萎縮における酸化ストレスの重要性, 第72回日本栄養・食糧学会大会, May 2018.
107.	Takeshi Nikawa : 無重力ストレスに対する初期応答酵素(アコニターゼ)の筋萎縮における役割, 2017年度生命科学系学会合同年次大会第40回日本分子生物学会年会，第90回日本生化学会大会, Dec. 2017.
108.	Takeshi Nikawa : Molecular mechanism of microgravity-induced muscle atrophy, 第65回国際歯科研究学会日本部会総会・学術大会, Nov. 2017.
109.	Miyuki Ninomiya, Hikaru Kishimoto, Ida Kurumi, Arisa Ochi, Kanako Kitahata, Marina Takagi, Ayako Maita, Shigetada Kondo, Tomoki Abe, 赤間一仁 and Takeshi Nikawa : 廃用性筋萎縮を防ぐ高機能米の開発, 第50回日本栄養・食糧学会中国・四国支部大会, Nov. 2017.
110.	Yukari Miki, Takayuki Uchida, Yuki Kimori, Yoshihiro Sakashita, Ayako Maita, Reiko Nakao, 小林剛, 東谷篤志, 石原直忠, 武田伸一, 曽我部正博 and Takeshi Nikawa : 無重力ストレスによる筋萎縮における酸化ストレスの重要性, 第50回日本栄養・食糧学会中国・四国支部大会, Nov. 2017.
111.	Hidehiro Umehara, Shinya Watanabe, Makoto Kinoshita, Yukiko Tomioka, Masahito Nakataki, 畠山豊, 中原潔, Takeshi Nikawa, Shusuke Numata and Tetsuro Ohmori : うつ病における血漿グルタミン，グルタミン酸，グルタミン/グルタミン酸比, 第27回日本臨床精神神経薬理学会, Nov. 2017.
112.	Akio Komatsu, Ayaka Tetsuno and Takeshi Nikawa : 無重力による筋細胞内シグナルトランスダクション, 第64回日本栄養改善学会学術総会, Sep. 2017.
113.	Ayaka Tetsuno, Akio Komatsu and Takeshi Nikawa : 癌カヘキシーによる筋萎縮を防ぐ機能性食材の創製, 第64回日本栄養改善学会学術総会, Sep. 2017.
114.	Takayuki Uchida, Ayako Maita, Reiko Nakao, 小林剛, 東谷篤志, 石原直忠, 武田伸一, 曽我部正博 and Takeshi Nikawa : 無重力ストレスによる筋萎縮における酸化ストレスの重要性, 日本筋学会第3回学術集会, Aug. 2017.
115.	Ayako Maita, Nobuo Maita, Yuushi Okumura, Hikaru Nagano, 有田恭平, Katsuya Hirasaka, Tomoki Abe, Shigetada Kondo and Takeshi Nikawa : 高病原性インフルエンザ感染に関わる宿主酵素MSPLと阻害ペプチドとの複合体構造, 第71回日本栄養・食糧学会大会, May 2017.
116.	Miyuki Ninomiya, Yuki Kimori, Marina Takagi, Kurumi Ida, Hikaru Kishimoto, Erika Takatsu, 石田祐子, 加藤健, Arisa Ochi, Takayuki Uchida, Ayako Maita, Tomoki Abe, Shigetada Kondo, Reiko Nakao, Katsuya Hirasaka and Takeshi Nikawa : 坐骨神経切除による筋萎縮におけるホエイペプチドと大豆タンパク質の阻害効果, 第71回日本栄養・食糧学会大会, May 2017.
117.	Takayuki Uchida, Yuki Kimori, Miyuki Ninomiya, Yoshihiro Sakashita, Tomoki Abe, Ayako Maita, Reiko Nakao, Katsuya Hirasaka, 東谷篤志, 小林剛, 曽我部正博, 武田伸一 and Takeshi Nikawa : 無重力による酸化ストレス産生を介した筋細胞内シグナル・トランスダクション, 第71回日本栄養・食糧学会大会, May 2017.
118.	Yuki Kimori, Miyuki Ninomiya, Chika Aihara, Yoshihiro Sakashita, Takayuki Uchida, Tomoki Abe, Reiko Nakao, Ayako Maita, Shigetada Kondo and Takeshi Nikawa : Mfn2ノックダウンの筋肉における影響の検討, 第71回日本栄養・食糧学会大会, May 2017.
119.	Takeshi Nikawa : 骨格筋蛋白質代謝と骨格筋量調節, 第20回日本病態栄養学会年次学術集会, Jan. 2017.
120.	Takeshi Nikawa : 海藻廃棄物からの次世代サルコペニア予防食の創製, 内閣府戦略的イノベーション創造プログラム(SIP)次世代農林水産業創造技術「次世代機能性農林水産物・食品の開発」公開シンポジウム∼夢の進展と社会実装, Dec. 2016.
121.	Ayako Maita, Nobuo Maita, Yuushi Okumura, Hikaru Nagano, Saki Tsugita, 有田恭平, 田畑考統, Katsuya Hirasaka, Tomoki Abe, Shigetada Kondo and Takeshi Nikawa : II型膜貫通型セリンプロテアーゼMSPLとペプチド性阻害剤との複合体結晶構造解析, 第39回日本分子生物学会年会, Dec. 2016. (Keyword) X-ray structure analysis / influenza
122.	相原可奈, Chisato Tomida, 山岸直子, 矢野千晶, Tomoki Abe, Ayako Maita, Takeshi Nikawa and Shigetada Kondo : 血管新生阻害薬によるがん細胞の悪性化機構の解明, 第39回日本分子生物学会年会, Nov. 2016.
123.	冨田知里, 山岸直子, 相原可奈, 矢野千晶, Tomoki Abe, Ayako Maita, Takeshi Nikawa and Shigetada Kondo : VEGF受容体阻害剤による大腸がん細胞悪性化の分子機構の解明, 第39回日本分子生物学会年会, Nov. 2016.
124.	矢野千晶, Chisato Tomida, 山岸直子, 相原可奈, Tomoki Abe, Ayako Maita, Takeshi Nikawa and Shigetada Kondo : アピゲニンによる大腸癌細胞悪性化の抑制とその分子機構の解明, 第39回日本分子生物学会年会, Nov. 2016.
125.	Takeshi Nikawa : Unloading環境による筋萎縮とその栄養学的治療法, 第23回アミノ酸セミナー:基礎と臨床を結ぶ会, Nov. 2016.
126.	二宮みゆき, 髙木麻理奈, 井田くるみ, 岸本ひかる, 高津絵梨香, 石田祐子, 加藤健, 越智ありさ, Takayuki Uchida, Ayako Maita, Tomoki Abe, Shigetada Kondo, Reiko Nakao, Katsuya Hirasaka and Takeshi Nikawa : 坐骨神経切除による筋萎縮に対するホエイペプチドと大豆タンパク質の効果, 第49回日本栄養・食糧学会中国・四国支部大会, Nov. 2016.
127.	小西明貴, Ayako Maita, Nobuo Maita, 次田早希, Tomoki Abe, Katsuya Hirasaka, Yuushi Okumura, Shigetada Kondo and Takeshi Nikawa : 廃用性筋萎縮原因酵素Cbl-bと阻害ペプチドCblinとの相互作用様式の解明, 第49回日本栄養・食糧学会中国・四国支部大会, Nov. 2016.
128.	Takeshi Nikawa : 寝たきりや無重力環境における筋蛋白質代謝とその制御による廃用性筋萎縮の治療法開発, 第31回日本整形外科学会基礎学術集会, Oct. 2016.
129.	Takeshi Nikawa : 筋蛋白質代謝改善のための栄養学的アプローチ, 第2回日本筋学会学術集会, Aug. 2016.
130.	Ayako Maita, Nobuo Maita, 次田早希, Tomoki Abe, Katsuya Hirasaka, Yuushi Okumura, Shigetada Kondo and Takeshi Nikawa : 廃用性筋萎縮原因酵素Cbl-bと阻害ペプチドCblinとの複合体結晶構造解析, 第21回日本病態プロテアーゼ学会学術集会, Aug. 2016.
131.	Takeshi Nikawa : 廃用性筋萎縮とユビキチンリガーゼ, 第21回日本病態プロテアーゼ学会学術集会, Aug. 2016.
132.	Takeshi Nikawa : Unloadingストレスによる筋細胞内シグナル・トランスダクション, 第34回日本骨代謝学会学術集会/第3回アジア太平洋骨代謝学会議, Jul. 2016.
133.	Takeshi Nikawa : 宇宙実験からわかった運動器(おもに筋)の新機能:重力センサーとしての働き, 健康寿命講座2016, Jun. 2016.
134.	Ayako Maita, Nobuo Maita, Yuushi Okumura, Hikaru Nagano, Saki Tsugita, 有田恭平, Aki Bandoh, 田畑考統, Katsuya Hirasaka, Tomoki Abe, Shigetada Kondo and Takeshi Nikawa : 高病原性インフルエンザウィルス感染に関わる宿主酵素MSPLとペプチド性阻害剤の複合体結晶構造, 第16回蛋白質科学会年会, Jun. 2016. (Keyword) X-ray structure analysis / influenza
135.	次田早希, Ayako Maita, 赤木謙一, Katsuya Hirasaka, Yuushi Okumura, Shigetada Kondo, Floriane Rudwill, Tomoki Abe, 杤尾豪人 and Takeshi Nikawa : The elucidation of the interaction betweeen UCP3 and HAX-1, 第16回日本蛋白質科学会年会, Jun. 2016.
136.	井田くるみ, 髙木麻理奈, 岸本ひかる, 越智ありさ, 北畑香菜子, 中尾玲子, 内田貴之, 矢野千晶, Ayako Maita, Tomoki Abe, Rudwii Froriane, Shigetada Kondo, Hisao Nemoto and Takeshi Nikawa : ユビキチンリガーゼCbl-b阻害による廃用性筋萎縮予防法の開発, 第70回日本栄養・食糧学会大会, May 2016.
137.	矢野千晶, 冨田知里, 山岸直子, 相原可奈, Tomoki Abe, Ayako Maita, Takeshi Nikawa and 近藤茂忠 : アピゲニンによる大腸癌細胞悪性化の抑制とその分子機構の解明, 第70回日本栄養・食糧学会大会, May 2016.
138.	内田貴之, 井田くるみ, 矢野千晶, Tomoki Abe, 真板(大野) 綾子 and Takeshi Nikawa : 無重力による筋細胞内シグナル・トランスダクション, 第70回日本栄養・食糧学会大会, May 2016.
139.	Takeshi Nikawa : 筋萎縮における細胞内シグナルとその制御による筋萎縮治療, 第70回日本栄養・食糧学会大会, May 2016.
140.	Takeshi Nikawa : 寝たきりや無重力による筋萎縮のメカニズム解明とその栄養学的治療法の開発, 第70回日本栄養・食糧学会大会, May 2016.
141.	Takeshi Nikawa : 廃用性筋萎縮改善ペプチド, 日本農芸化学会2016年度大会, Mar. 2016.
142.	Katsuya Hirasaka and Takeshi Nikawa : IGF-1シグナル経路の活性化を介した廃用性筋萎縮予防法, 第30回宇宙環境利用シンポジウム, Jan. 2016.
143.	山田明徳 and Takeshi Nikawa : 無重力や宇宙放射線の筋細胞における転写への影響, 精神・神経疾患研究開発費「筋ジストロフフィーモデル動物を用いた新たな治療法の開発」平成27年度武田班班会議, Dec. 2015.
144.	冨田知里 and Takeshi Nikawa : VEGF阻害薬による大腸がん細胞の悪性化とその分子機構の解明, 第38回日本分子生物学会年会, Dec. 2015.
145.	相原可奈 and Takeshi Nikawa : 血管新生阻害薬によるがん細胞の悪性化機構の解明, 第38回日本分子生物学会年会, Dec. 2015.
146.	矢野千晶 and Takeshi Nikawa : アピゲニンによる大腸癌細胞悪性化の抑制とその分子機構の解明, 第38回日本分子生物学会年会, Dec. 2015.
147.	Takeshi Nikawa : 無重力ストレスに対する筋細胞の応答機構, 第42回日本臨床バイオメカニクス学会, Nov. 2015.
148.	井田くるみ and Takeshi Nikawa : 廃用性筋萎縮を防ぐ高機能米の開発, 第48回日本栄養・食糧学会中国・四国支部大会, Nov. 2015.
149.	坂下禎宏 and Takeshi Nikawa : 無重力による筋細胞のシグナル・トランスダクション, 第48回日本栄養・食糧学会中国・四国支部大会, Nov. 2015.
150.	次田早希 and Takeshi Nikawa : Hax-1とUCP3の相互作用様式の解明, 第48回日本栄養・食糧学会中国・四国支部大会, Nov. 2015.
151.	Takeshi Nikawa : 筋萎縮を予防・治療できる新規機能性食材の開発, 第7回「栄養とエイジング」国際会議プログラム, Sep. 2015.
152.	Takeshi Nikawa : 骨格筋萎縮に対抗する新たな栄養学的アプローチ:タンパク質分解から酸化ストレスへ Novel nutritional approarches against skeletal muscle atrophy: From proteolysis to oxdative stress, International Symposium on Dietary Antioxidants and Oxidative Stress in Health, Aug. 2015.
153.	Takeshi Nikawa : ビタミンDと筋肉, 第1回Neo Vitamin D Workshop学術集会, Aug. 2015.
154.	Floriane Rudwill and Takeshi Nikawa : Consequences of a 21-d bed rest on lipid metabolism in humans and effect of protein supplementation tested as a countermeasure, 第1回Neo Vitamin D Workshop学術集会, Aug. 2015.
155.	Takeshi Nikawa : 廃用性筋萎縮の分子メカニズムとその栄養学的治療法の開発, 日本食品科学工学会第62回大会, Aug. 2015.
156.	Takeshi Nikawa : Unloading-mediated signal transduction in skeletal muscle cells, 12th Meeting of Bone Biology Forum, Aug. 2015.
157.	次田早希 and Takeshi Nikawa : UCP3とHax-2の相互作用様式の解明, 第20回日本病態プロテアーゼ学会学術集会, Aug. 2015.
158.	高木麻里奈 and Takeshi Nikawa : 廃用性筋萎縮を防ぐユビキチン化ぺプチドCblin(Cbl-b inhibitor)の高機能化, 第20回日本病態プロテアーゼ学会学術集会, Aug. 2015.
159.	内田貴之 and Takeshi Nikawa : 無重力ストレスによる筋細胞内シグナル・トランスダクション, 第1回日本筋学会学術集会, Aug. 2015.
160.	岸本ひかる and Takeshi Nikawa : 廃用性筋萎縮を防ぐ高機能米の開発, 第1回日本筋学会学術集会, Aug. 2015.
161.	Takeshi Nikawa : 筋萎縮の分子メカニズムとその栄養学的治療法, 日本アミノ酸学会第6回夏のシンポジウム, Jul. 2015.
162.	Takeshi Nikawa, 越智ありさ, 高木麻里奈, 北畑香菜子, Tomoki Abe, Ayako Maita, Shigetada Kondo and 赤間一仁 : 無重力による筋細胞のシグナルトランスダクションと筋萎縮, 日本農芸化学会2015年度大会, Mar. 2015.
163.	Takeshi Nikawa : 宇宙医学:宇宙飛行に伴う医学的問題，筋萎縮とその対策, 第120回日本解剖学会総会・全国学術集会,第92回日本生理学会大会合同大会, Mar. 2015.
164.	Takeshi Nikawa : 無重力による筋萎縮のメカニズムとそれに有効な機能性食材の開発, 日本栄養改善学会関東・甲信越支部第2回学術総会, Feb. 2015.
165.	冨田知里, 山岸直子, 相原可奈, 矢野千晶, Tomoki Abe, Ayako Maita, Katsuya Hirasaka, Shigetada Kondo and Takeshi Nikawa : 血管新生阻害薬による大腸がん細胞の悪性化とその分子機構の解明, 第37回日本分子生物学会年会, Nov. 2014.
166.	Chieko Shiota, Tomoki Abe, Nobuhiko Kawai, Chieko Shiota, Takeshi Nikawa and Eiji Tanaka : LPS誘導性筋萎縮関連遺伝子発現を抑制しうるフラボノイドの探索とその抑制機構の解明, 第73回日本矯正歯科学会大会プログラム・抄録集, 212, Oct. 2014.
167.	Nobuhiko Kawai, Katsuya Hirasaka, Natsuko Hichijo, Chieko Shiota, Hiroyo Mori, Nao Kinouchi, Takeshi Nikawa and Eiji Tanaka : アテロコラーゲンを担体とした抗ユビキチン化ペプチドによる骨格筋萎縮抑制法の開発, 第73回日本矯正歯科学会大会プログラム・抄録集, 209, Oct. 2014.
168.	Takeshi Nikawa : 骨格筋の微小重力ストレス感知機構, 第87回日本生化学会, Oct. 2014.
169.	Takeshi Nikawa : 無重力環境での筋蛋白質代謝と栄養, 第61回日本栄養改善学会学術総会, Aug. 2014.
170.	Rie Mukai, 松井直子, Takeshi Nikawa and Junji Terao : ケルセチンはミトコンドリアの機能を保つことで廃用性筋萎縮を予防する, 第8回日本ポリフェノール学会学術大会, Aug. 2014.
171.	Yuushi Okumura, 宇都宮健郎, 永野ひかる, Tomoki Abe, Ayako Maita, Shigetada Kondo and Takeshi Nikawa : Myostatin活性化を標的としたプロテアーゼ阻害剤はステロイド性筋萎縮を抑制する, 第19回日本病態プロテアーゼ学会学術集会, Aug. 2014.
172.	Takeshi Nikawa : 無重力や加齢による筋萎縮とユビキチンリガーゼ, 第14回日本抗加齢医学会総会, Jun. 2014.
173.	Takeshi Nikawa : 廃用性筋萎縮とサルコぺニアの分子メカニズム:筋ユビキチンリガーゼの役割, 第55回日本神経学会学術大会, May 2014.
174.	Takeshi Nikawa : Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading, International Symposium on Mechanobiology 2014, May 2014.
175.	堀川瞳, Rie Mukai, 河村知志, Takeshi Nikawa and Junji Terao : プレニルナリンゲニンは廃用性筋萎縮からの筋量回復を促進する, 第18回日本フードファクター学会学術集会, Nov. 2013.
176.	Tomoki Abe, Katsuya Hirasaka, 越智ありさ, Ayako Maita, Shigetada Kondo and Takeshi Nikawa : ユビキチンリガーゼCbl-bによるインスリン抵抗性発症抑制機構の解明, 第34回日本肥満学会, Oct. 2013.
177.	tomoki abe, Katsuya Hirasaka, arisa Ochi, Ayako Maita, Shigetada Kondo and Takeshi Nikawa : ユビキチンリガーゼCbl-bによるインスリン抵抗性発症抑制機構の解明, 第34回日本肥満学会, Oct. 2013.
178.	Nobuhiko Kawai, Katsuya Hirasaka, Natsuko Hichijo, Chieko Shiota, Hiroyo Mori, Nao Kinouchi, Takeshi Nikawa and Eiji Tanaka : 抗ユビキチン化ペプチドによる骨格筋萎縮抑制法の開発, 第72回日本矯正歯科学会大会プログラム・抄録集, Oct. 2013.
179.	Nobuhiko Kawai, Katsuya Hirasaka, Chieko Shiota, 越智ありさ, Tomoki Abe, Ayako Maita, Shigetada Kondo, Eiji Tanaka and Takeshi Nikawa : アテロコラーゲンを担体とした抗ユビキチン化ペプチドによる骨格筋萎縮抑制, 日本宇宙生物科学会第27回大会, Sep. 2013.
180.	Takeshi Nikawa : 廃用性筋萎縮の分子メカニズムとその治療法開発を中心に, 第1回筋骨格系リサーチワークショップ, Sep. 2013.
181.	Takeshi Nikawa : 宇宙生活での健康上の問題点 -宇宙生物学・宇宙医学の視点より-, 第53回日本化学会年次学術集会, Sep. 2013.
182.	Tomoki Abe, Katsuya Hirasaka, 越智ありさ, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : ユビキチンリガーゼCbl-bと脂肪組織浸潤マクロファージの活性化, 第18回日本病態プロテアーゼ学会学術集会, Aug. 2013.
183.	tomoki abe, Katsuya Hirasaka, arisa Ochi, hikawaru nagano, tasuku maeda, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : ユビキチンリガーゼCbl-bと脂肪組織浸潤マクロファージの活性化, 第18回日本病態プロテアーゼ学会学術集会, Aug. 2013.
184.	Katsuya Hirasaka, Mills M Edward., 池田千佳, 春名真理江, 前田翼, Tomoki Abe, 宇都宮健郎, 越智ありさ, 河野尚平, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : サルコぺニアにおけるミトコンドリア内カルシウム取り込み, 第67回日本栄養・食糧学会大会, May 2013.
185.	Tomoki Abe, Katsuya Hirasaka, 越智ありさ, 永野ひかる, 前田翼, 坂東亜紀, Ayako Maita, Shigetada Kondo and Takeshi Nikawa : 肥満脂肪組織におけるCbl-bの役割, 第67回日本栄養・食糧学会大会, May 2013.
186.	永野ひかる, Shigetada Kondo, 山岸直子, 数藤拓郎, 冨田知里, 坂井敦子, Tomoki Abe, 宇都宮健郎, 越智ありさ, 池田千佳, 後藤春樹, 山下結衣, 坂東亜紀, 前田翼, Ayako Maita, Katsuya Hirasaka, Yuushi Okumura and Takeshi Nikawa : IRS-1遺伝子産物による骨格筋細胞の分化制御, 第67回日本栄養・食糧学会大会, May 2013.
187.	Takeshi Nikawa : 「廃用性筋萎縮改善ペプチド」, 第67回日本栄養・食糧学会大会, May 2013.
188.	tomoki abe, Katsuya Hirasaka, arisa Ochi, hikawaru nagano, tasuku maeda, Ayako Maita, Shigetada Kondo and Takeshi Nikawa : 肥満脂肪組織におけるCbl-bの役割, 第67回日本栄養・食糧学会大会, May 2013.
189.	Katsuya Hirasaka, Mills M. Edward., chika Ikeda, marie haruna, tasuku maeda, tomoki abe, kenro utsunomiya, arisa ochi, shohei khono, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : サルコペニアにおけるミトコンドリア内カルシウム取り込み, 第67回日本栄養・食糧学会大会, May 2013.
190.	Aki Bando, Ayako Maita, hidehito tochio, Haruka Maeyama, Katsuya Hirasaka, Chika Ikeda, marie haruna, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : UCP3結合領域を介したHAX-1とCa2+の相互作用解析, 第67回日本栄養・食糧学会大会, May 2013.
191.	前田翼, Katsuya Hirasaka, 池田千佳, 春名真理江, 河野尚平, Tomoki Abe, 越智ありさ, Shigetada Kondo, Ayako Maita, Yuushi Okumura and Takeshi Nikawa : SIRT1発現上昇を介したイソフラボンによるサルコぺニア抑制効果, 第67回日本栄養・食糧学会大会, May 2013.
192.	tasuku maeda, Katsuya Hirasaka, chika ikeda, marie haruna, syohei kohno, tomoki abe, arisa ochi, Shigetada Kondo, Ayako Maita, Yuushi Okumura and Takeshi Nikawa : SIRT1発現上昇を介したイソフラボンによるサルコペニア抑制効果, 第67回日本栄養・食糧学会大会, May 2013.
193.	arisa Ochi, haruki Gtoh, kanako kitahata, Tomoki Abe, Ayako Maita, Katsuya Hirasaka, Shigetada Kondo, kazuhito akama and Takeshi Nikawa : 廃用性筋萎縮を防ぐ抗ユビキチン化ペプチドCblin(Cbl-b Inhibitor)を含む機能性食材の開発, 第67回日本栄養・食糧学会大会, May 2013.
194.	松井直子, Rie Mukai, 候徳興, 河村知志, Hisao Nemoto, Takeshi Nikawa and Junji Terao : 酸化ストレス上昇を伴う廃用性筋萎縮に対する抗酸化プレニルケルセチンの効果, 第67回本栄養食糧学会, May 2013.
195.	Takeshi Nikawa : 卵白由来のプロテアーゼ阻害成分による筋萎縮予防法の開発, 第1回タマゴシンポジウム, May 2013.
196.	atsuko sakai, hisayo hamada, keiko hara, kyoko mori, takashi mizuguchi, jyun mizuguchi, syu kawashima and Takeshi Nikawa : 外来血液透析患者に対する4年間の継続指導の効果, 第66回日本栄養・食糧学会大会, May 2013. (Keyword) 血液透析 / 栄養指導
197.	Takeshi Nikawa : 「脂肪組織浸潤マクロファージとインスリン抵抗性」, 第86回日本内分泌学会学術総会, Apr. 2013.
198.	marie haruna, chika ikeda, Katsuya Hirasaka, tasuku maeda, arisa ochi, tomoki abe, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : UCP3とHax-3の相互作用によるミトコンドリアのカルシウム濃度の調節, 第45回日本栄養・食糧学会中国・四国支部大会, Nov. 2012.
199.	tasuku maeda, Katsuya Hirasaka, chika ikeda, marie haruna, syohei kohno, tomoki abe, arisa ochi, hikaru nagano, Shigetada Kondo, Ayako Maita, Yuushi Okumura and Takeshi Nikawa : 加齢による筋萎縮に対する大豆ポリフェノールの効果, 第45回日本栄養・食糧学会中国・四国支部大会, Nov. 2012.
200.	堀川瞳, Rie Mukai, 藤倉温, 河村知志, Hisao Nemoto, Takeshi Nikawa and Junji Terao : 坐骨神経切除マウスにおける8-プレニルナリンゲニンの廃用性筋萎縮抑制効果, 第17回日本フードファクター学会学術集会第9回日本カテキン学会総会合同大会 2012, Nov. 2012.
201.	tomiki abe, Katsuya Hirasaka, syohei kohno, arisa ochi, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : 肥満脂肪組織におけるCbl-bによるマクロファージ活性化調節機構, 第33回日本肥満学会, Oct. 2012.
202.	Takeshi Nikawa : 寝たきりや無重力による筋萎縮の分子メカニズム, 第34回薬効解析学研究室セミナー, May 2012.
203.	Arisa Ochi, Reiko Nakao, Yoriko Yamamoto, Katsuya Hirasaka, Shigetada Kondo, keisuke nagano, Hisao Nemoto, kazuhito akama and Takeshi Nikawa : 廃用性筋萎縮を防ぐ抗ユビキチン化ペプチドCblin(Cbl-b inhibitor)の高機能化, 第66回日本栄養・食糧学会大会, May 2012.
204.	tomoki abe, Katsuya Hirasaka, syohei kohno, arisa ochi, yui yamashita, chika ikeda, Shigetada Kondo, Ayako Maita, Yuushi Okumura and Takeshi Nikawa : 脂肪細胞におけるCbl-bによるマクロファージ活性化制御機構, 第66回日本栄養・食糧学会大会, May 2012.
205.	Takeshi Nikawa : 廃用性筋萎縮の分子メカニズムとその栄養学的治療, 第66回日本栄養・食糧学会大会, May 2012.
206.	hikaru nagano, Shigetada Kondo, syohei kohno, atsuko sakai, tomoki abe, kenro utsunomiya, arisa ochi, tastuya ueji, tastuya ueji, keita kannmura, chika ikeda, haruki goto, yui yamashita, aki bando, tasuku maeda, takurou suto, Ayako Maita, Katsuya Hirasaka, Yuushi Okumura and Takeshi Nikawa : IRS-1遺伝子産物による骨格筋細胞の分化制御, 第66回日本栄養・食糧学会大会, May 2012.
207.	Rie Mukai, 堀川瞳, 河村知志, Hisao Nemoto, Takeshi Nikawa and Junji Terao : プレニル化フラボノイドによる廃用性筋萎縮の予防, 第66回日本栄養・食糧学会大会, May 2012.
208.	Yamashita Yui, Kohno Shohei, Abe Tomoki, Katsuya Hirasaka, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : Unloading stress disturbs muscle regeneration through perturbed recruitment and function of macrophages, 第34回日本分子生物学年会, Dec. 2011.
209.	Kohno Shohei, Shigetada Kondo, Katsuya Hirasaka, Abe Tomoki, Ayako Maita, Higashitani Atsushi, Akira Higashibata, Kobayashi Takeshi, Yuushi Okumura, Sokabe Masahiro and Takeshi Nikawa : Mitochondria is a master signal inducer for unloading stress toward muscle atrophy, 第34回日本分子生物学年会, Dec. 2011.
210.	Abe Tomoki, Katsuya Hirasaka, Kagawa Sachiko, Kohno Shohei, Ochi Arisa, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : Cbl-b is a critical regulator of macrophage activation associated with obesity-induced insulin resistance in mice, 第34回日本分子生物学年会, Dec. 2011.
211.	Ochi Arisa, Nakao Reiko, Ueji Tatsuya, Katsuya Hirasaka, Ayako Maita, Shigetada Kondo, Yuushi Okumura, Nagano Keisuke, Hisao Nemoto, Akama Kazuhito and Takeshi Nikawa : High functionalization of anti-ubiquitination oligopeptide, Cblin:Cbl-b inhibitor that prevents unloading-induced skeletal muscle atrophy, 第34回日本分子生物学年会, Dec. 2011.
212.	上村啓太, 越智ありさ, 数藤拓郎, 中尾玲子, Katsuya Hirasaka, Yuushi Okumura, Shigetada Kondo and Takeshi Nikawa : Dex誘導性筋萎縮に対するCblin(Cbl-b inhibitor)の作用, 第57回日本宇宙航空環境医学会大会, Nov. 2011.
213.	後藤春樹, 越智ありさ, 中尾玲子, 上地達也, Ayako Maita, Katsuya Hirasaka, Yuushi Okumura, Shigetada Kondo, 長野圭介, Hisao Nemoto, 赤間一仁 and Takeshi Nikawa : 抗ユビキチン化ペプチドCblin(Cbl-b inhibitor)を含む機能性食材の開発, 日本アミノ酸学会第5回学術大会, Nov. 2011.
214.	安倍知紀, Katsuya Hirasaka, 河野尚平, 山下結衣, 中尾玲子, Ayako Maita, Shigetada Kondo, Yuushi Okumura, 青山敏明 and Takeshi Nikawa : 骨格筋の脂肪酸酸化への中鎖脂肪酸の作用, 第65回日本栄養・食糧学会大会, May 2011.
215.	乙敬宏, 尾脇加奈子, 鈴木瑛里, 矢野桃子, Yuushi Okumura, Ayako Maita, Shigetada Kondo, Katsuya Hirasaka, Akiko Harada and Takeshi Nikawa : Unloadingストレス下における筋固有の応答機構:オステオアクチビン分子の動態と役割について, 第65回日本栄養・食糧学会大会, May 2011.
216.	山下結衣, 河野尚平, 安倍知紀, Katsuya Hirasaka, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : 骨格筋再生における機械的負荷の重要性, 第65回日本栄養・食糧学会大会, May 2011.
217.	上村啓太, 山智成, 中尾玲子, 越智ありさ, 数藤拓郎, Katsuya Hirasaka, Ayako Maita, Yuushi Okumura, Shigetada Kondo, 石堂一巳 and Takeshi Nikawa : 大豆由来ペプチドを用いた廃用性筋萎縮に有効な食材の開発, 第65回日本栄養・食糧学会大会, May 2011.
218.	越智ありさ, 中尾玲子, 上地達也, Ayako Maita, Katsuya Hirasaka, Yuushi Okumura, Shigetada Kondo, 長野圭介, 河村知志, Hisao Nemoto, 赤間一仁 and Takeshi Nikawa : 抗ユビキチン化ペプチドCblin(Cbl-b inhibitor)を含む機能性食材の開発, 第65回日本栄養・食糧学会大会, May 2011.
219.	河野尚平, Shigetada Kondo, Katsuya Hirasaka, Ayako Maita, Yuushi Okumura, 中尾玲子, Akira Higashibata, 東谷篤志 and Takeshi Nikawa : 廃用性筋萎縮の発生機序∼オミクス技術を用いた無重力応答因子の探索, 第65回日本栄養・食糧学会大会, May 2011.
220.	Rie Mukai, 水口八重子, 藤倉温, 河野尚平, Takeshi Nikawa, Yoshichika Kawai and Junji Terao : ケルセチンの経口摂取による廃用性筋萎縮予防の可能性, 第65回日本栄養・食糧学会大会, May 2011.
221.	上地達也, 白方あゆみ, 越智ありさ, 乙敬宏, 河野尚平, 長野圭介, Akiko Harada, Ayako Maita, Yuushi Okumura and Takeshi Nikawa : IRS-1のユビキチン化阻害ペプチドとCbl-bの相互作用解析, 第33回日本分子生物学会年会, Dec. 2010. (Keyword) protein / structure / Cbl-b
222.	Takeshi Nikawa : 無重力や寝たきりによる筋萎縮の分子メカニズム, 第43回日本栄養・食糧学会中国・四国支部大会, Nov. 2010.
223.	Takeshi Nikawa : 抗ユビキチン化ペプチドと廃用性筋萎縮, 第6回機能性宇宙食研究会, Nov. 2010.
224.	安倍知紀, Katsuya Hirasaka, 河野尚平, 加川祥子, 市川雅子, Akiko Harada, Ayako Maita, Yuushi Okumura and Takeshi Nikawa : Cbl-bは肥満脂肪組織における炎症反応及びインスリン抵抗性発症を防ぐ, 日本肥満学会第31回, Oct. 2010.
225.	Akiko Harada, 松尾侑季, 古賀友紀, 河野尚平, Katsuya Hirasaka, Yuushi Okumura, Yutaka Nakaya and Takeshi Nikawa : SPORTSラットを用いた長距離走行が可能な骨格筋の糖代謝, 日本肥満学会第31回, Oct. 2010.
226.	Takeshi Nikawa : 寝たきりによる筋萎縮に対する予防食材としての大豆ペプチドの有効性, 大豆のはたらきin 徳島, Oct. 2010.
227.	矢野桃子, 水野智子, 吉田和香奈, 尾脇加奈子, 乙敬宏, 鈴木瑛里, Yuushi Okumura, Ayako Maita, Akiko Harada and Takeshi Nikawa : Unloading 環境下におけるMyostatin 活性化機構, 日本宇宙生物科学会第24回大会, Sep. 2010.
228.	山智成, 上村啓太, 越智ありさ, Katsuya Hirasaka, Ayako Maita, Yuushi Okumura, Akiko Harada, 石堂一巳 and Takeshi Nikawa : 廃用性筋萎縮に対する予防食材としての大豆ペプチドの有効性, 日本宇宙生物科学会第24回大会, Sep. 2010.
229.	越智ありさ, 中尾玲子, 山智成, 上村啓太, Katsuya Hirasaka, Ayako Maita, Yuushi Okumura, Akiko Harada, 長野圭介, 片桐綾人, 河村知志, Hisao Nemoto, Ken-ichi Miyamoto and Takeshi Nikawa : 抗ユビキチン化ペプチドCblin (Cbl-b inhibitor)の高機能化, 日本アミノ酸学会第4回学術大会, Sep. 2010.
230.	Takeshi Nikawa : Jミルク招待講演, Aug. 2010.
231.	Rie Mukai, Takeshi Nikawa and Junji Terao : 廃用性筋萎縮に伴う酸化ストレス上昇に対するケルセチンの効果, 第63回日本酸化ストレス学会学術集会, Jun. 2010.
232.	越智ありさ, 中尾玲子, 山智成, 上村啓太, 古谷順也, Ayako Maita, Yuushi Okumura, Akiko Harada, 長野圭介, 片桐綾人, 河村知志, 根元尚夫, Ken-ichi Miyamoto and Takeshi Nikawa : 廃用性筋委縮を防ぐ抗ユビキチン化ペプチドの開発, 第64回日本栄養・食糧学会大会, May 2010.
233.	山智成, 中尾玲子, 上村啓太, 越智ありさ, Katsuya Hirasaka, Ayako Maita, Yuushi Okumura, Akiko Harada, 石堂一巳 and Takeshi Nikawa : 廃用性筋萎縮に対する予防食材としての大豆ペプチドの有効性, 第64回日本栄養・食糧学会大会, May 2010.
234.	矢野桃子, 吉田和香奈, 尾脇加奈子, 乙敬宏, Yuushi Okumura, Ayako Maita, Akiko Harada and Takeshi Nikawa : 骨格筋における無重力感知の分子機構:ユビキチンリガーゼCbl-bの発現調節について, 第64回日本栄養・食糧学会大会, May 2010.
235.	尾脇加奈子, 乙敬宏, 矢野桃子, 吉田和香奈, Yuushi Okumura, Ayako Maita, Akiko Harada and Takeshi Nikawa : Unloadingストレス下における生体反応機構:オステオアクチビンの発現調節と作用機序について, 第64回日本栄養・食糧学会大会, May 2010.
236.	松尾侑季, Akiko Harada, 古賀友紀, Ayako Maita, Katsuya Hirasaka, Yuushi Okumura, Yutaka Nakaya and Takeshi Nikawa : 持久的な運動に適した骨格筋における糖代謝, 第64回日本栄養・食糧学会大会, May 2010.
237.	河野尚平, 上地達也, Katsuya Hirasaka, Akiko Harada, Ayako Maita, Yuushi Okumura and Takeshi Nikawa : ユビキチンリガーゼCbl-b遺伝子欠損による骨格筋再生の遅延, 第64回日本栄養・食糧学会大会, May 2010.
238.	安倍知紀, Katsuya Hirasaka, 加川祥子, 河野尚平, 中尾玲子, 市川雅子, Ayako Maita, Akiko Harada, Yuushi Okumura and Takeshi Nikawa : Cbl-bは高脂肪食によるマクロファージの活性化を抑制し，インスリン抵抗性発症を防ぐ, 第64回日本栄養・食糧学会大会, May 2010.
239.	Arisa Ochi, Reiko Nakao, Tomonari Yama, Keita Kammura, Junya Furutani, Ayako Maita, Yuushi Okumura, Akiko Harada, 長野圭介, 片桐綾人, Hisao Nemoto, Ken-ichi Miyamoto and Takeshi Nikawa : 廃用性筋萎縮を防ぐ抗ユビキチン化ペプチドの開発, 第64回日本栄養・食糧学会大会, May 2010.
240.	片桐彩人, 神谷昌樹, 河村知志, Hisao Nemoto, 吉富康亮, 服部初彦, 中尾玲子, Takeshi Nikawa and Hisao Nemoto : 抗ユビキチン化作用を有するペンタペプチドのBGL化と活性評価, 日本薬学会第130年会, Mar. 2010.
241.	Rie Mukai, 藤倉温, Takeshi Nikawa, Hironori Yamamoto, Eiji Takeda and Junji Terao : 廃用性筋萎縮モデルマウスにおけるケルセチンの筋重量低下抑制効果, 日本農芸化学会2010年度大会, Mar. 2010.
242.	Rie Mukai, 中尾玲子, Takeshi Nikawa, Hironori Yamamoto, Eiji Takeda and Junji Terao : マウス尾懸垂モデル系におけるケルセチンの筋萎縮抑制効果, 第14回日本フードファクター学会学術集会, Nov. 2009.
243.	田中亜紀, 香川恵子, Kazuyoshi Kawazoe, Takeshi Nikawa, Junji Terao and Kazuo Minakuchi : 栄養学的指標に基づく漢方薬の医薬品としての品質評価, 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, 164, Nov. 2008.
244.	田中亜紀, Kazuyoshi Kawazoe, Takeshi Nikawa, Junji Terao and Kazuo Minakuchi : 栄養学的指標に基づく漢方薬の評価研究, 日本薬学会年会, Mar. 2008.
245.	河野尚平, Katsuya Hirasaka, 加川祥子, 中尾玲子, Kazuaki Mawatari, Nagakatsu Harada, Yutaka Nakaya, 石堂一巳, Yousuke Ebina, Kyoichi Kishi and Takeshi Nikawa : Cbl-b遺伝子欠損によるマクロファージの活性化を介した耐糖能異常, 第19回分子糖尿病学シンポジウム, Dec. 2007.

Et cetera, Workshop:

1.	Takeshi Nikawa : 無重力による筋萎縮の分子メカニズムとその栄養学的予防法の開発, Science Pioneers Consortium 2020, Dec. 2020.
2.	Takeshi Nikawa : 廃用性筋萎縮と食成分, 第22回健康栄養シンポジウム「筋肉と食の科学 ∼健康長寿に繋げる最新研究∼」, Feb. 2020.
3.	Takeshi Nikawa : 国際宇宙ステーション実験からえたUnloadingによる筋萎縮の分子メカニズム, 第18回糖尿病運動療法研究会 2nd STAGE, Jan. 2020.
4.	Takeshi Nikawa : 無重力による筋萎縮の分子メカニズムとその栄養学的治療法, 第6回スペース・コロニー講演会, Jul. 2019.
5.	Takeshi Nikawa : 宇宙実験から得た抗筋萎縮栄養法，高齢者への応用, 第6回臨床栄養実践協会設立記念セミナー, Apr. 2019.
6.	Takeshi Nikawa : 機能性宇宙食の開発, 平成30年度宇宙基地医学研究会, Feb. 2019.
7.	Takeshi Nikawa, Takayuki Uchida, Ayako Maita, Reiko Nakao, Katsuya Hirasaka, 小林剛, 曽我部正博, 東谷篤志 and 武田伸一 : 廃用性筋萎縮における酸化ストレスの重要性, 国立研究開発法人国立精神・神経医療研究センター精神・神経疾患研究開発費「ジストロフィン欠損モデル動物を基盤とした筋ジストロフィーの新しい治療法開発」平成30年度班会議, Dec. 2018.
8.	Takeshi Nikawa, Akira Takahashi, Katsuyuki Miyawaki and Yoshihiro Deguchi : 無重力や寝たきりによる筋萎縮の分子メカニズムとその栄養学的アプローチ, ナノオプティクス研究グループ第25回研究討論会, Nov. 2018.
9.	Takeshi Nikawa : 無重力による廃用性筋萎縮におけるROSの重要性, 第19回運動器科学研究会, Sep. 2018.
10.	Takeshi Nikawa : 無重力や寝たきりによる筋萎縮の分子メカニズムとその栄養学的治療法, 広島修道大学健康科学部開設記念講演会, Mar. 2018.
11.	Takeshi Nikawa, Takayuki Uchida, Ayako Maita, Reiko Nakao, 小林剛, 曽我部正博 and 武田伸一 : 無重力(Unloading)ストレスによる筋細胞のシグナルトランスダクション, 国立研究開発法人国立精神・神経医療研究センター精神・神経疾患研究開発費「ジストロフィン欠損モデル動物を基盤とした筋ジストロフィーの新しい治療法開発」平成29年度班会議, Dec. 2017.
12.	Takeshi Nikawa : ユビキチンリガーゼCbl-bの阻害ペプチド(Cblin)の抗筋萎縮効果, 第51回機能性食品用ペプチド研究会∼ペプチドによる筋萎縮予防の可能性∼, Oct. 2017.
13.	Takeshi Nikawa : 宇宙医学・栄養学∼無重力による筋萎縮のメカニズムと次世代サルコペニア予防食の創製, ''未来へのバイオ技術''勉強会「宇宙とバイオ」, Sep. 2017.
14.	Takeshi Nikawa, Takayuki Uchida, Ayako Maita and Reiko Nakao : 無重力環境で培養した筋細胞のメタボローム解析, 第2回メタボローム解析シンポジウム, Jun. 2017.
15.	Hidehiro Umehara, Shinya Watanabe, Makoto Kinoshita, Yukiko Tomioka, Masahito Nakataki, 畠山豊, 中原潔, Takeshi Nikawa, Shusuke Numata and Tetsuro Ohmori : うつ病のメタボローム解析, 第2回メタボローム解析シンポジウム, Jun. 2017.
16.	Takeshi Nikawa : 抗老化たん白質源としての大豆たん白質食の臨床試験に向けて∼ホエイたん白質食との相加効果と大豆たん白質の抗酸化作用∼, 公益財団法人不二たん白質研究振興財団第20回研究報告会(平成28年度助成課題), May 2017.
17.	Takeshi Nikawa : 坐骨神経切除による筋萎縮に対する大豆たん白質およびホエイたん白質の効果, 公益財団法人不二たん白質研究振興財団第19回研究報告会(平成27年度助成課題), May 2016.
18.	Nobuhiko Kawai, Takeshi Nikawa and Eiji Tanaka : 抗ユビキチン化ペプチドによる骨格筋萎縮抑制, Mar. 2016.
19.	Katsuya Hirasaka, chika ikeda, marie haruna, tasuku maeda, tomoki abe, kenro utsunomiya, arisa ochi, Ayako Maita, Shigetada Kondo, Yuushi Okumura, shinichi takeda and Takeshi Nikawa : 加齢による筋萎縮におけるミトコンドリア内カルシウム取り込み機構, 精神・神経疾患研究開発費「筋ジストロフーに対するトランスレーショナル・リサーチ」平成24年度武田班班会議, Dec. 2012.
20.	Takeshi Nikawa, shohei kohno, yui yamashita, tomoki abe, Katsuya Hirasaka, Shigetada Kondo, Ayako Maita, ikuya nonaka, shinichi takeda, keisuke nagano and Yuushi Okumura : 寝たきりや無重力による筋萎縮のメカニズムとその治療法の開発, 精神・神経疾患研究開発費「筋ジストロフーに対するトランスレーショナル・リサーチ」平成24年度武田班班会議, Dec. 2012.
21.	池田千佳, Katsuya Hirasaka, 前田翼, 河野尚平, 安倍知紀, Shigetada Kondo, Ayako Maita, Yuushi Okumura and Takeshi Nikawa : 筋特異的ミトコンドリア膜蛋白質UCP3の新規結合蛋白質の同定, 第44回日本栄養・食糧学会中国・四国支部大会, Nov. 2011.
22.	河野尚平, Katsuya Hirasaka, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : 廃用性筋萎縮発症の分子メカニズム, 第12回運動器科学研究会, Sep. 2011.
23.	Katsuya Hirasaka, 河野尚平, Ayako Maita, Shigetada Kondo, Yuushi Okumura and Takeshi Nikawa : ミトコンドリア由来酸化ストレスの筋特異的制御機構, 第12回運動器科学研究会, Sep. 2011.
24.	Takeshi Nikawa : 大豆セリンプロテアーゼ阻害剤による廃用性筋萎縮の治療∼骨格筋のセリンプロテアーゼ型ストレスセンサーの発見, (財)不二たん白質研究振興財団第13回(平成21年度助成研究課題)研究報告会, May 2010.
25.	Takeshi Nikawa, Kyoichi Kishi, 埜中征哉, 武田伸一, 木南英紀, 石堂一巳, 弓削類 and Keeneth M. Baldwin : Cbl-mediated protein ubiquitination downregulates the response of skeletal muscle cells to growth factors in space, 第4回国際宇宙ステーション利用研究テーマの国際公募採択実験, 2002. (Summary) 第4回国際宇宙ステーション実験の国際公募に採択された．無重力により発現の増大するユビキチン結合酵素の病理的役割を解明する．平成19年に宇宙ステーションで実験を行う予定である．
26.	Natsuo Yasui, Koichi Sairyo, Takeshi Nikawa and Kyoichi Kishi : Osteoactivin : A novel glycoprotein inhibiting adhesion of osteoblastic cells to bone matrix, ラット宇宙実験サンプルシェア研究, 2002. (Summary) 今夏に打ち上げ予定のスペースシャトルでの実験の国際公募に採択された．本実験では宇宙ラットの骨サンプルを用い新規接着性蛋白質であるオステオアクチビンの機能を研究する予定である．
27.	Natsuo Yasui, Koichi Sairyo, Takeshi Nikawa and Kyoichi Kishi : 無重力環境における骨萎縮の分子メカニズム:宇宙遊泳ラットを用いた骨関連遺伝子解析, 文部科学省科学研究費萌芽研究, 2002. (Summary) 宇宙フライトにより萎縮した大腿骨を用い，骨萎縮に関連する遺伝子群をDNAマイクロアレイ法で解析する．
28.	Natsuo Yasui, 高田信二郎, Shunji Nakano, Takeshi Nikawa and Koichi Sairyo : 仮骨延長術における骨リモデリング機構の解明, 文部科学省科学研究費基盤研究B, 2002. (Summary) 仮骨延長術における機械的ストレスが骨細胞，骨芽細胞，破骨細胞にどのような影響をあたえているのかについて分子レベルで解明し，より進展効率のよい仮骨延長術を開発する．
29.	Kyoichi Kishi, Takeshi Nikawa and Kazuhito Rokutan : 無重力により変動する筋肉内遺伝子群をターゲットとした新しい筋肉保護食品(剤)の開発, 文部科学省科学研究費基盤研修C, 2001. (Summary) DNAマイクロアレイ技術を用いて，宇宙環境の筋肉遺伝子の発現を地上と同じ状態に保たせることができる栄養素や薬剤を見出す．
30.	Takeshi Nikawa, Kyoichi Kishi, Kazuhito Rokutan and 柴原進 : N末端法則を用いたジペプチドによる筋内ユビキチン蛋白質分解系の制御とその臨床応用, 文部科学省科学研究費基盤研究C, 2001. (Summary) 筋蛋白質のユビキチンープロテアソーム依存性蛋白質分解の抑制に最も効果のあるジペプチドを発見する．
31.	Takeshi Nikawa, Kyoichi Kishi, Kazuhito Rokutan, Shigetada Teshima, 埜中征哉 and 武田伸一 : 無重力により発現の変動する新規筋肉内遺伝子の解析, 日本宇宙フォーラム公募地上研究, 2000. (Summary) 宇宙フライトにより発現の変化する遺伝子をDNAマイクロアレイ法で解析し，それらの筋萎縮における役割を検討した．
32.	Kyoichi Kishi, Kazuhito Rokutan, Takeshi Nikawa and Shigetada Teshima : 廃用性萎縮筋におけるミトコンドリア遺伝子の発現異常とその栄養学的改善法, 文部省科学研究費基盤研究C, 1999. (Summary) 廃用性萎縮筋におけるミトコンドリア遺伝子の発現異常を明らかにし，廃用性筋萎縮の予防法の開発を目指した．
33.	Takeshi Nikawa : IL-5受容体欠損マウスを用いた小腸粘膜でのIL-5とビタミンAの相互作用の解析, 文部省科学研究費奨励研究A, 1998. (Summary) IL-5受容体欠損マウスを用い，IL-5とビタミンAの相互作用による新しい小腸粘膜免疫の活性化機構を研究した．
34.	Kyoichi Kishi, Takeshi Nikawa, Kazuhito Rokutan and 埜中征哉 : 無重力による筋萎縮に有効な宇宙食の開発, 日本宇宙フォーラム公募地上研究, 1997.
35.	Takeshi Nikawa, Kyoichi Kishi, Kazuhito Rokutan and 埜中征哉 : 蛋白質分解酵素阻害剤による無重力下の筋萎縮および骨粗鬆症の治療, 日本宇宙フォーラム公募地上研究, 1997. (Summary) 無重力による骨萎縮と筋萎縮ともに蛋白質分解酵素が関与する．蛋白質分解酵素阻害剤のこれら疾患の治療薬として有効性を検証した．
36.	Kyoichi Kishi, Kazuhito Rokutan, 木戸康博 and Takeshi Nikawa : 微小重力環境下の筋萎縮の予防に対する栄養学的アプローチ, 日本宇宙環境利用推進センターフロンティア共同研究, 1996. (Summary) 筋蛋白質の合成・分化や筋細胞の増殖・分化に及ぼす食事の効果を調べ，筋萎縮の予防に有効な栄養法の開発を目指した．
37.	Kyoichi Kishi, Kazuhito Rokutan, 木戸康博 and Takeshi Nikawa : 脳微小透析法による非特異的栄養素摂取調節構の解明, 文部省科学研究費一般研究C, 1996. (Summary) 脳微小透析法を用い，蛋白質，糖質，脂質それぞれの摂取調整機序を追求した．
38.	Takeshi Nikawa and Kazuhito Rokutan : サイトカインを介した小腸特異酵素の発現とその分子機構, 文部省科学研究費一般研究C, 1996. (Summary) レチノイン酸存在下でサイトカインを介した小腸特異酵素の発現のメカニズムを研究した．
39.	Kyoichi Kishi, Kazuhito Rokutan and Takeshi Nikawa : 運動による筋傷害の成因とその予防に対する栄養学的アプローチ, 文部省科学研究費一般研究C, 1988. (Summary) 急性運動障害で重要な働きをしているカルパインに焦点をあて，それを阻害できる栄養素を探求した．

Report:

1.	Yoshihiko Ueno, Yosuke Seki, Ryuji Yorioka, Yuishin Izumi, Takeshi Nikawa, Reiko Okahisa, Naozumi Ishimaru, Kazumi Ozaki, Hideji TANAKA, Kenji Terada, Tamotsu Tanaka, Ray S. Furuya and Maiko Kamioka : 令和3年度徳島大学高等教育研究センターアドミッション部門報告書, 令和3年度徳島大学高等教育研究センターアドミッション部門報告書, Mar. 2022.
2.	Yoshihiko Ueno, Yosuke Seki, Kenji Sato, Masako Nomaguchi, Takeshi Nikawa, Hitoshi Ikushima, Kenichi Hamada, Yasuhiko Shirayama, Ken-ichi Yamada, Akihiro Furube, Hitoshi Matsuki, Ray S. Furuya and Maiko Kamioka : 平成30年度徳島大学総合教育センターアドミッション部門報告書, 平成30年度徳島大学総合教育センターアドミッション部門報告書, Tokushima, Mar. 2019.
3.	Yoshihiko Ueno, Maiko Sawada, Tatsuro Aratake, Ichiro Hashimoto, Takeshi Nikawa, Toshiyuki Yasui, Kenichi Hamada, Yasuhiko Shirayama, Ken-ichi Yamada, Masahide Hojo, Takeshige Otoi, Ray S. Furuya and Yosuke Seki : 平成29年度徳島大学総合教育センターアドミッション部門報告書, 平成29年度徳島大学総合教育センターアドミッション部門報告書, Mar. 2018.
4.	Takeshi Nikawa : ラット骨格筋遺伝子の宇宙フライトによる発現変動, 必須アミノ酸研究, Vol.170, 49-53, Jul. 2004.
5.	Takeshi Nikawa, 平坂勝也, 加納美保子, 浅野間友紀, 水澤典子, Kazuhito Rokutan, Kyoichi Kishi, 小川貴之, Natsuo Yasui, 池本円, 武田伸一 and 埜中征哉 : 宇宙フライトラットの骨格筋で発現の増大する新規遺伝子Sfigのフローニング, 必須アミノ酸研究, Vol.166, 1-6, Mar. 2003.
6.	Masayuki Shibuya, Hiroshi Kido, Yoshio Hayashi, Hisao Nemoto, Shigeki Sano, Koji Yasutomo, Hiroyuki Azuma, Yasuhiko Nishioka, Junji Terao, Takeshi Nikawa, Hiroaki Misawa, Shigeki Matsuo, Yoshinobu Baba, Kozo Matsumoto, Hirokazu Miyoshi and Saburo Sone : 徳島大学先端医療開発研究センター設置準備室成果報告書, Dec. 2002.
7.	Takeshi Nikawa, 池本円, 平坂勝也, 加納美保子, 山本多恵子, 田中礼子, 鎌田まり子, Kazuhito Rokutan and Kyoichi Kishi : 尾部懸垂による筋肉内酸化ストレスと筋蛋白質のユビキチン化に対するシステインの阻害効果, 必須アミノ酸研究, Vol.164, 56-61, May 2002.
8.	Takeshi Nikawa, Madoka Ikemoto, Chiho Watanabe, Takako Kitano, Keeneth M. Baldwin, Ryutaro Izumi, Ikuya Nonaka, Shigetada Teshima, Kazuhito Rokutan, Shinichi Takeda and Kyoichi Kishi : Development of effective space food against weightlessness-induced muscle atrophy, The Progress Report of Ground Research Announcement for Space Utilization, Dec. 2001.
9.	Takeshi Nikawa, 池本円, 加納美保子, 平坂勝也, 武田伸一, Keeneth M. Baldwin, 埜中征哉 and 石堂一巳 : Effects of space shuttle flight on gene expresson in rat skeletal muscle, Biol Sei Space, Vol.15, No.3, 312-313, Oct. 2001.
10.	Takeshi Nikawa, 池本円, 北野貴子, 加納美保子, 香川和代, 武田伸一, 埜中征哉, 泉龍太郎, Keeneth M. Baldwin, Shigetada Teshima, Kazuhito Rokutan and Kyoichi Kishi : 微少重力環境下の骨格筋における蛋白質分解とプロテアーゼの発現, Space Utilization Research, Vol.17, 7-9, May 2001.
11.	Takeshi Nikawa, 北野貴子, 池本円, Shigetada Teshima, Kazuhito Rokutan, Kyoichi Kishi, 泉龍太郎, Keeneth M. Baldwin and 武田伸一 : 重力により発現の変動する新規筋肉内遺伝子の解析, 必須アミノ酸研究所, Vol.158, 61-65, Aug. 2000.
12.	Kyoichi Kishi, Takeshi Nikawa, 池本円, 渡辺千穂, 北野貴子, Keeneth M. Baldwin, 泉龍太郎, 埜中征哉, Shigetada Teshima, Kazuhito Rokutan and 武田伸一 : 無重力による筋萎縮に有効な宇宙食の開発, 宇宙環境利用に関する公募地上研究(平成10年度終了分)成果報告書, 241-258, Jul. 2000.
13.	森永寛子, Shigetada Teshima, 佐藤光恵, 近藤和美, Takeshi Nikawa, Kyoichi Kishi and Kazuhito Rokutan : 新規アレルギー関連サイトカイン(IgE依存症ヒスタミン放出因子)産出に及ぼすM-CSFの役割, Ther Res, Vol.21, No.S1, S26-S2, May 2000.
14.	Kyoichi Kishi, Kazuhito Rokutan, Takeshi Nikawa and Shigetada Teshima : タンパク質必要量算定の現状と問題点, 必須アミノ酸研究, Vol.156, 1-8, Dec. 1999.
15.	Kazuhito Rokutan, Tomoko Kawai, 森永寛子, 佐藤光恵, 楠本健二, 河原司, 近藤和美, Takeshi Nikawa and Kyoichi Kishi : タンパク質栄養と熱ショック応答, 必須アミノ酸研究, Vol.156, 12-19, Dec. 1999.
16.	Takeshi Nikawa, 池本円, 渡辺千穂, 北野貴子, Shigetada Teshima, Kazuhito Rokutan and Kyoichi Kishi : 微小重力による筋萎縮とタンパク質分解酵素, 必須アミノ酸研究, Vol.155, 37-59, Nov. 1999.
17.	Takeshi Nikawa, 池本円, 渡辺千穂, 北野貴子 and Shigetada Teshima : アニオン(O^2-)の産生とその生理的役割, Ther Res, Vol.20, No.s1, s66-s70, May 1999.
18.	Tomoko Kawai, Kazuhito Rokutan, Takeshi Nikawa and Kyoichi Kishi : 急性ストレス負荷時の胃粘膜におけるストレス蛋白質の誘導のメカニズムとその生理作用について, Cyto-protection Biol, Vol.16, 13-16, Dec. 1998.
19.	新田早美, 米原小枝, Kazuhito Rokutan, Takeshi Nikawa and Kyoichi Kishi : 高脂肪食投与ラットの体脂肪蓄積に及ぼす大豆タンパク質と運動の効果, 必須アミノ酸研究, Vol.152, 71-76, Oct. 1998.
20.	Shigetada Teshima, Kazuhito Rokutan, Takeshi Nikawa and Kyoichi Kishi : マクロファージコロニー刺激因子によるIgE依存症ヒスタミン放出因子の誘導, Ther Res, Vol.19, No.S1, S166-S169, May 1998.
21.	Shigetada Teshima, Kazuhito Rokutan, 三好真美, 平川哲也, Takeshi Nikawa and Kyoichi Kishi : レドックス感受性転写因子NF-κBによる胃粘膜上皮細胞の酸化ストレス応答, Ther Res, Vol.18, No.S1, 185-189, May 1997.
22.	木戸康博, 岡田邦彦, 小田原賢二, Takeshi Nikawa, Kazuhito Rokutan and Kyoichi Kishi : ラット腸粘膜IgA量に及ぼすタンパク質欠乏とコレラ毒素の影響, 必須アミノ酸研究, Vol.146, 40-46, Nov. 1996.
23.	Takeshi Nikawa, Shigetada Teshima, 坂井敦子, 木戸康博, Kyoichi Kishi, Kazuhito Rokutan and David H. Alpers : レチノイン酸による小腸上皮細胞株の分化誘導, Ther Res 1996, Vol.17, No.S1, S125-S129, May 1996.
24.	平川哲也, Kazuhito Rokutan, Shigetada Teshima, Takeshi Nikawa, 木戸康博 and Kyoichi Kishi : ストレスたん白質の誘導におよぼす大豆たん白質の影響, 大豆たん白質研究会会誌, Vol.16, 4-8, Osaka, Dec. 1995.
25.	平川哲也, 山田昌彦, Shigetada Teshima, 坂井敦子, 山本孝, Takeshi Nikawa, 木戸康博, Kyoichi Kishi and Kazuhito Rokutan : 胃粘膜細胞のストレス反応の分子機構:グルタチオンによるストレス蛋白質遺伝子の転写調節について, Ther Res, Vol.16, No.S1, 173-177, May 1995.
26.	Takeshi Nikawa, 山本孝, 山内有信, 大野誉子, 難波佳世, 木戸康博, Kyoichi Kishi and Kazuhito Rokutan : 運動に伴うフリーラジカル傷害の抑制に対する大豆たん白質の効果, 大豆たん白質研究会会誌, Vol.15, 45-50, Osaka, Dec. 1994.

Patent:

1.	Takeshi Nikawa, Yuushi Okumura and Ayako Maita : MSPL特異的阻害剤，及び高病原性インフルエンザウイルス感染又は，増殖抑制用組成物, 2018-126822 (Jul. 2018), .

Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)

Effect of exosome-like nanoparticles derived from marine products and its mechanism on health promotion (Project/Area Number: 23K10939 )
Elucidation of metabolic regulation in muscle cells by cancer-derived exosomes to overcome cancer cachexia (Project/Area Number: 23K06613 )
New function linkage between dietary protein and skeletal muscle via small intestine-derived exosomes (Project/Area Number: 22H03513 )
Effects of metabolic syndrome on locomotor function and the mechanism of exercise therapy. (Project/Area Number: 20K09435 )
Effect of marine carotenoids against muscle atrophy and its mechanism (Project/Area Number: 19K11792 )
Development of a Novel Therapy for Cancer Cachexia by Targeting Metabolic Changes in Skeletal muscle (Project/Area Number: 19K07731 )
Mechano-nutrition-signaling for disuse muscle atrophy (Project/Area Number: 19H04054 )
Exosome-mediated muscle atrophy and new therapeutic approaches for cancer cachexia (Project/Area Number: 19H03516 )
Sensing system of microgravity in muscle mitochondria (Project/Area Number: 18H04981 )
ユビキチン-プロテアソーム系制御による廃用性筋萎縮抑制法の開発 (Project/Area Number: 17K11938 )
Identification of mitochondrial aconitase as a critical enzyme sensitive to microgravity stress (Project/Area Number: 16H01645 )
Molecular rehabilitation of mitochondrial function towards preventing muscle atrophy (Project/Area Number: 15H04960 )
Elucidation of a novel evasive adaptation mechanism against antiangiogenic treatment in colorectal cancer cells (Project/Area Number: 15H04931 )
Development of the treatment of the skeletal muscle atrophy through the IGF-1 signaling in the growth period (Project/Area Number: 26463095 )
Effect of functional marine flavonoid on muscle atrophy (Project/Area Number: 26350148 )
Molecular genetic analysis of atherosclerosis and atrial thrombosis rat model spontaneously induced by hypoactivity (Project/Area Number: 25560368 )
Identification of novel proteases involved in the regulation of highly pathogenic avian influenza (HPAI) viruses infection (Project/Area Number: 24591481 )
Mitochondria is a key signal inducer for unloading stress toward muscle atrophy (Project/Area Number: 24390355 )
Rapid screening of gene(s) related to the phenotype of model rats with high levels of voluntarily wheel running activity (Project/Area Number: 23650406 )
Pathological analysis for loss ofmuscle contraction after tendon transfer surgery (Project/Area Number: 22591658 )
骨格筋萎縮を予防する抗ユビキチン化オリゴペプチドの開発 (Project/Area Number: 21659355 )
Medium chain fatty acid regulates uncoupling protein 3 expression in skeletal muscle (Project/Area Number: 21590257 )
Molecular mechanisms of muscle mass regulation : Identification of a novel protease involved in myostatin activation. (Project/Area Number: 21500632 )
新規筋代謝マーカーの確立-運動療法の実効度・リスク度の簡易評価法の開発- (Project/Area Number: 20500579 )
Enhancement of bone healing during distraction osteogenesis (Project/Area Number: 20390401 )
Basic research on the integrated regulation of locomotive function (Project/Area Number: 20249064 )
筋ジス治療薬としてのエピガロカテキンガレートの適格性と分子作用機序の研究 (Project/Area Number: 19591208 )
Molecular meohanisms of mechanosensing inskeletal muscles : Based on regulation system of atrogen expression (Project/Area Number: 19500564 )
Development of oligopeptides against skeletal muscle fatigue and atrophy caused by unloading (Project/Area Number: 18590218 )
Musculo-skeletal regeneration during distracionosteogenesis (Project/Area Number: 18390418 )
Thrombin and mast cell tryptase are trigger proteases in arthritis. (Project/Area Number: 17591577 )
Characterization of a cerebellar ubiquitin ligase, which mediates effects of training to nerve (Project/Area Number: 17500430 )
Does the collagen IX tryptophan polymorphism trigger lumbar disc degeneration? (Project/Area Number: 16591496 )
A muscle secreting protein attractin regulates expression of UCP-2 in adipocytes. (Project/Area Number: 16590175 )
Modulation of Bone Remodeling during Distraction Osteogenesis (Project/Area Number: 16390441 )
Clarification of the pathophysiological significance of mast cell tryptase and protease activated receptor-2 (PAR-2) in articular destruction (Project/Area Number: 15591581 )
Design, synthesis and property of peptide mimics having inhibition effect of reducing musclar strength (Project/Area Number: 15510177 )
Molecular mechanism of unloading-mediated insulin resistance (Project/Area Number: 15500449 )
無重力環境における骨萎縮の分子メカニズム (Project/Area Number: 14657368 )
BONE REMODELING IN THE CALLUS FORMED DURING -DISTRACTION OSTEOGENESIS (Project/Area Number: 14370465 )
Inhibition of N-end rule-dependent proteolysis by dipeptide (Project/Area Number: 13670065 )
Development of novel nutritional methods to inhibit muscle atrophy caused by microgravity. (Project/Area Number: 13660126 )
Abmormal expression of mitochondrial gene in disuse-induced muscle atrophy (Project/Area Number: 11670071 )
IL-5受容体欠損マウスを用いた小腸粘膜でのIL-5とビタミンAの相互作用の解析 (Project/Area Number: 10770232 )
Synergistic effects of retinoic acid and IL-1beta on expression of the bone-type alkaline phsphatase and retinoid receptors in small intestinal epithelial cells. (Project/Area Number: 08670599 )
脳微小透析法による非特異的栄養素摂取調節機構の解明 (Project/Area Number: 08670084 )
運動による筋傷害の成因とその予防に対する栄養学的アプローチ (Project/Area Number: 07670084 )
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Professor : Nikawa, Takeshi

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Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)