The role of mitochondria ion channels in the estrogen-induced cardioprotection.

线粒体离子通道在雌激素诱导的心脏保护中的作用。

• 批准号: 17590707
• 负责人: SATO Toshiaki
• 金额: $ 2.24万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590707/
• 关键词: estrogen; mitochondria; Ca^<2+>-activated K^+ channel; testosterone; ATP-sensitive K^+ channel; cardiomyocytes; Ca^<2+>

Estrogen has been shown to protect the hearts against ischemia/reperfusion injury, but little is known of underlying mechanism. This study was undertaken to know the role of mitochondrial ion channels in estrogen-induced cardioprotection. We measured the flavoprotein fluorescence in isolated rabbit ventricular myocytes to assay mitochondrial ATP-sensitive K^+ (mitoK_<ATP>) channel and mitochondrial Ca^<2+>-activated K^+(mitoK_<Ca>) channel activity. The results of this investigation are as follows.(1) Estrogen reversibly oxidized flavoprotein fluorescence. This effect of estrogen was completely inhibited by the mitoK_<Ca> channel blocker paxilline, but not by the mitoK_<ATP> channel blocker 5-hydroxydecanoate. These results indicate that estrogen opens mitoK_<Ca> channels.(2) Testosterone reversibly oxidized flavoprotein fluorescence. This effect of testosterone was inhibited by the mitoK_<ATP> channel blocker 5-hydroxydecanote, but not by the mitoK_<Ca> channel blocker paxilline. These results indicate that testosterone activates mitoK_<ATP> channels.(3) Estrogen augmented the testosterone-induced flavoprotein oxidation when applied after the effect of testosterone had reached steady state.These results taken together suggest that estrogen activates mitoK_<Ca> channels whereas testosterone activates mitoK_<ATP> channels. It has been shown that opening of mitoK_<Ca> and K_<ATP> channels attenuates mitochondrial Ca^<2+> overload. Therefore, the combined effects of estrogen and testosteron suggest that mitochondrial K^+ through the distinct types of channels occurs independently of each other and then confers cardioprotection in a similar manner.

雌激素已被证明可以保护心脏免受缺血/再灌注损伤，但其机制尚不清楚。本研究旨在了解线粒体离子通道在雌激素诱导的心肌保护中的作用。本研究通过测定兔心室肌细胞黄素蛋白荧光，分析线粒体ATP敏感性钾<ATP>通道和线粒体Ca^&lt;2+&gt;激活性<Ca>钾通道的活性。调查结果如下。(1)雌激素可逆氧化黄素蛋白荧光。雌激素的这种作用可被mitoK_<Ca>通道阻断剂paxilline完全阻断，但不能被mitoK_<ATP>通道阻断剂5-hydroxydecanoate阻断。这些结果表明，雌激素开放<Ca>mitoK_2通道。(2)四环素可逆氧化黄素蛋白荧光。睾酮的这种作用可被mitoK<ATP>通道阻断剂5-hydroxydecanote所抑制，但不被mitoK<Ca>通道阻断剂paxilline所抑制。这些结果表明，睾酮激活<ATP>mitoK_2通道。(3)当睾酮作用达到稳态后再给予雌激素，雌激素可增强睾酮诱导的黄素蛋白氧化，这些结果表明雌激素激活<Ca>mitoK_2通道，而睾酮激活<ATP>mitoK_2通道。线粒体K_2<Ca>和K_2<ATP>通道的开放可减轻线粒体Ca^&lt;2+&gt;超载。因此，雌激素和睾酮的联合作用表明，线粒体K^+通过不同类型的通道相互独立地发生，然后以类似的方式赋予心脏保护作用。

项目成果

分子標的を目指した不整脈治療.

针对分子靶点的心律失常治疗。

• 发表时间: 2005
• 期刊: 最新医学10 特集不整脈における分子機構 60・10
• 作者: Suzuki H;Momoi N;Ono T;Maeda S;Shikama Y;Matsuoka I;Suzuki H;Kimura J.;Fan Yu-Yan;金井 好克;中谷晴昭
• 通讯作者: 中谷晴昭

T細胞のアポトーシスにおけるClC-3BCl^-チャネルの役割の解析.

ClC-3BCl^-通道在T细胞凋亡中的作用分析。

• 发表时间: 2005
• 期刊: 上原記念生命科学財団研究報告集 19
• 作者: Yamazaki S;Iwama A;Takayanagi SI;Morita Y;Eto K;Ema H;Nakauchi H.;中谷晴昭
• 通讯作者: 中谷晴昭

心不全に伴うイオンチャンネルのリモデリングとその治療戦略.

心力衰竭相关的离子通道重塑及其治疗策略。

• 发表时间: 2006
• 期刊: 医学のあゆみ 心不全UPDATE 218・14
• 作者: Shimokawa N;Londono M;Koibuchi N;浅野 敏;Akira Matsuura;赤塚結子;Nishida H.;Yasuda N.;Nishida A.;中谷晴昭;中谷晴昭;中谷晴昭;中谷晴昭;中谷晴昭;中谷晴昭;Fujita H.;Yamashita Y.;Sato T.;中谷晴昭
• 通讯作者: 中谷晴昭

Prostacyclin attenuates oxidative damage of myocytes by opening mitochondrial ATP-sensitive K+ channels via the EP3 receptor

• DOI: 10.1152/ajpheart.01003.2004
• 发表时间: 2005-05-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
• 影响因子: 4.8
• 作者: Shinmura, K;Tamaki, K;Bolli, R
• 通讯作者: Bolli, R

Kir6.2-deficient mice are susceptible to stimulated ANP secretion:: KATP channel acts as a negative feedback mechanism?

• DOI: 10.1016/j.cardiores.2005.03.011
• 发表时间: 2005-07-01
• 期刊: CARDIOVASCULAR RESEARCH
• 影响因子: 10.8
• 作者: Saegusa, N;Sato, T;Nakaya, H
• 通讯作者: Nakaya, H