| Project/Area Number |
17590707
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
SATO Toshiaki Chiba University, Graduate School of Medicine, Associate Professor, 大学院医学研究院, 助教授 (60244159)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYA Haruaki Chiba University, Graduate School of Medicine, Professor, 大学院医学研究院, 教授 (60113594)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | estrogen / mitochondria / Ca^<2+>-activated K^+ channel / testosterone / ATP-sensitive K^+ channel / cardiomyocytes / Ca^<2+> |
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| Research Abstract |
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.
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