misc
"タイトル(日本語)","タイトル(英語)","著者(日本語)","著者(英語)","担当区分","概要(日本語)","概要(英語)","出版者・発行元(日本語)","出版者・発行元(英語)","出版年月","誌名(日本語)","誌名(英語)","巻","号","開始ページ","終了ページ","記述言語","査読の有無","招待の有無","掲載種別","国際・国内誌","国際共著","DOI","ISSN","eISSN","URL","URL2","主要な業績かどうか","公開の有無"
"酸化ストレス制御を基盤とする新規心腎血管障害治療薬の開発","Drug development for cardiorenal disease based on oxidative stress control","今西 正樹, 石澤 啓介, 櫻田 巧, 石澤 有紀, 山野 範子, 木平 孝高, 池田 康将, 土屋 浩一郎, 玉置 俊晃","Masaki Imanishi, Keisuke Ishizawa, TAKUMI SAKURADA, Yuki Izawa-Ishizawa, Noriko Yamano, Yoshitaka Kihira, Yasumasa Ikeda, Koichiro Tsuchiya, Toshiaki Tamaki","null","Oxidative stress is a key factor involved in the pathogenesis and progression of cardiovascular disease (CVD) and chronic kidney disease (CKD). Reactive oxygen species (ROS), produced as a result of redox reactions in various cells, have been recognized as key chemical mediators causing cellular damage and organ dysfunction in CVD and CKD. Nifedipine, a well-known calcium channel blocker, is extremely sensitive to light which gets converted to its nitroso analog, nitrosonifedipine (NO-NIF) in the presence of ultraviolet and visible light. The so formed NO-NIF blocks calcium channel quite weakly compared to that of nifedipine. However, we elucidated for the first time that NO-NIF is converted to NO-NIF radical which acquires extremely strong antioxidant property via reaction with unsaturated fatty acid or endothelial cells. We have already reported that NO-NIF reduces the cytotoxicity of cumene hydroperoxide, which hampers the integrity of cell membrane through oxidative stress, in endothelial cells. Additionally, we demonstrated that NO-NIF restored acetylcholine-responsive vascular relaxation and suppressed intercellular adhesion molecule-1 expression in the aorta of N(ω)-nitro-L-arginine methyl ester-treated rats, a model of vascular endothelial dysfunction. Recently, we reported that NO-NIF ameliorates angiotensin II-induced vascular remodeling via antioxidative effects in vivo and in vitro. These observations point towards the plausible, unique role of NO-NIF as a novel antioxidant which improves vascular dysfunction for overcoming CVD and CKD and the same has been highlighted in this review.","Oxidative stress is a key factor involved in the pathogenesis and progression of cardiovascular disease (CVD) and chronic kidney disease (CKD). Reactive oxygen species (ROS), produced as a result of redox reactions in various cells, have been recognized as key chemical mediators causing cellular damage and organ dysfunction in CVD and CKD. Nifedipine, a well-known calcium channel blocker, is extremely sensitive to light which gets converted to its nitroso analog, nitrosonifedipine (NO-NIF) in the presence of ultraviolet and visible light. The so formed NO-NIF blocks calcium channel quite weakly compared to that of nifedipine. However, we elucidated for the first time that NO-NIF is converted to NO-NIF radical which acquires extremely strong antioxidant property via reaction with unsaturated fatty acid or endothelial cells. We have already reported that NO-NIF reduces the cytotoxicity of cumene hydroperoxide, which hampers the integrity of cell membrane through oxidative stress, in endothelial cells. Additionally, we demonstrated that NO-NIF restored acetylcholine-responsive vascular relaxation and suppressed intercellular adhesion molecule-1 expression in the aorta of N(ω)-nitro-L-arginine methyl ester-treated rats, a model of vascular endothelial dysfunction. Recently, we reported that NO-NIF ameliorates angiotensin II-induced vascular remodeling via antioxidative effects in vivo and in vitro. These observations point towards the plausible, unique role of NO-NIF as a novel antioxidant which improves vascular dysfunction for overcoming CVD and CKD and the same has been highlighted in this review.","null","null","2014-06","薬学雑誌","Journal of the Pharmaceutical Society of Japan","Vol.134","No.6","715","719","jpn","null","null","introduction_scientific_journal","null","null","10.1248/yakushi.13-00255-4","1347-5231","null","null","null","null","null"
"Nitrosonifedipineはangiotensin IIによるマウス血管リモデリングを抑制する","Nitrosonifedipineはangiotensin IIによるマウス血管リモデリングを抑制する","櫻田 巧, 石澤 啓介, 今西 正樹, 藤井 聖子, 谷口 順平, 石澤 有紀, 宮本 理人, 木平 孝高, 池田 康将, 冨田 修平, 水口 和生, 土屋 浩一郎, 玉置 俊晃","櫻田 巧, Keisuke Ishizawa, Masaki Imanishi, 藤井 聖子, 谷口 順平, Yuki Izawa-Ishizawa, Licht Miyamoto, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Kazuo Minakuchi, Koichiro Tsuchiya, Toshiaki Tamaki","null","null","null","null","null","2013-01-10","腎とフリーラジカル","腎とフリーラジカル","Vol.11","null","78","81","jpn","null","null","introduction_scientific_journal","null","null","null","null","null","null","null","null","null"
"インスリン抵抗性による血管障害の細胞内情報伝達機構","Intracellular signal transduction of vascular injury in insulin resistance","吉栖 正典, 石澤 啓介, 井澤 有紀, 玉置 俊晃","Masanori Yoshizumi, Keisuke Ishizawa, Yuki Izawa, Toshiaki Tamaki","null","近年,メタボリック症候群の疾患概念が確立され,本邦でもその診断基準が発表された.メタボリック症候群の根底にはインスリン抵抗性が存在するといわれるが,高血圧,動脈硬化などの血管病にインスリン抵抗性がどのように関っているかは未だ明らかではない.我々はこの数年,血管病の発症,進展に関わるインスリン抵抗性の細胞内情報伝達機構について研究を行なってきた.糖尿病モデル動物のOLETFラットを用いた検討では,アンジオテンシンII受容体拮抗薬の投与が末梢での糖利用臓器のインスリン抵抗性を改善させ,レニン-アンジオテンシン系のメタボリック症候群への関与が示唆された.培養血管平滑筋細胞を用いた細胞内情報伝達機構の検討では,アンジオテンシンII刺激によって活性化されるMAPキナーゼの一つ,ERK1/2がインスリン抵抗性の発現に関与していることが明らかになった.また,血管リモデリング進展過程のひとつである血管平滑筋細胞の遊走において,SrcチロシンキナーゼやCasアダプタータンパクが細胞内分子として重要な役割を果たしていることを見いだした.血管病におけるインスリン抵抗性に関わる標的分子の探求は,今後も増加することが予想されるメタボリックシンドローム治療のための創薬に有用な情報をもたらすことが期待される.
","近年,メタボリック症候群の疾患概念が確立され,本邦でもその診断基準が発表された.メタボリック症候群の根底にはインスリン抵抗性が存在するといわれるが,高血圧,動脈硬化などの血管病にインスリン抵抗性がどのように関っているかは未だ明らかではない.我々はこの数年,血管病の発症,進展に関わるインスリン抵抗性の細胞内情報伝達機構について研究を行なってきた.糖尿病モデル動物のOLETFラットを用いた検討では,アンジオテンシンII受容体拮抗薬の投与が末梢での糖利用臓器のインスリン抵抗性を改善させ,レニン-アンジオテンシン系のメタボリック症候群への関与が示唆された.培養血管平滑筋細胞を用いた細胞内情報伝達機構の検討では,アンジオテンシンII刺激によって活性化されるMAPキナーゼの一つ,ERK1/2がインスリン抵抗性の発現に関与していることが明らかになった.また,血管リモデリング進展過程のひとつである血管平滑筋細胞の遊走において,SrcチロシンキナーゼやCasアダプタータンパクが細胞内分子として重要な役割を果たしていることを見いだした.血管病におけるインスリン抵抗性に関わる標的分子の探求は,今後も増加することが予想されるメタボリックシンドローム治療のための創薬に有用な情報をもたらすことが期待される.
","null","null","2006-09-01","日本薬理学雑誌","Folia Pharmacologica Japonica","Vol.128","No.3","147","151","jpn","null","null","introduction_scientific_journal","null","null","10.1254/fpj.128.147","0015-5691","null","http://ci.nii.ac.jp/naid/10018399832/","null","null","null"