2001 Fiscal Year Final Research Report Summary
Role of mitochondrial ATP-sensitive potassium channels in apoptosis
Project/Area Number |
12670681
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
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Research Institution | OITA MEDICAL UNIVERSITY |
Principal Investigator |
YONEMOCHI Hidetoshi OITA MEDICAL UNIVERSITY, MEDICAL DEPARTMENT, ASSOCIATED PROFESSOR, 医学部, 助教授 (40191671)
|
Co-Investigator(Kenkyū-buntansha) |
SATO Toshiaki CHIBA UNIVERSITY, GRADUATED SCHOOL OF MEDICINE, ASSOCIATED PROFESSOR, 大学院・医学研究院, 助教授 (60244159)
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Project Period (FY) |
2000 – 2001
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Keywords | Cardioprotection / apoptosis / K^+ channel / mitochondria / ischemia |
Research Abstract |
Although mitochondrial ATP-sensitive potassium (mitoK_<ATP>) channels have been reported to reduce the extent of apoptosis, the critical timing of mitoK_<ATP> channel opening required to protect myocytes against apoptosis remains unclear. In the present study, we examined whether the mitoK_<ATP> channel serves as a trigger of cardioprotection against apoptosis induced by oxidative stress. Apoptosis of cultured neonatal rat cardiomyocytes was determined by flow cytometry (light scatter and propidium iodide/annexin V-FITC fluorescence) and by nuclear staining with Hoechst 33342. Mitochondrial membrane potential (ΔΨ) was measured by flow cytometry of cells stained with rhodamine-123 (Rh-123). Exposure to H_2O_2 (500 μM) induced apoptosis and the percentage of apoptotic cells increased progressively and peaked at 2 hours. This H_2O_2-induced apoptosis was associated with the loss of ΔΨ, and the time-course of decrease in Rh-123 fluorescence paralleled that of apoptosis. Pretreatment of cardiomyocytes with diazoxide (100 μM), a putative mitoK_<ATP> channel opener, for 30 min prior to exposure to H_2O_2 elicited the transient and mild depolarization of AW, and consequently suppressed both apoptosis and ΔΨ loss after 2 hours exposure to H_2O_2. These protective effects of diazoxide were abrogated by the, mitoKATP channel blocker 5-hydroxydecanoate (500 μM), but not by the sarcolemmal K_<ATP> channel blocker HMR 1098 (30 μM). Our results suggest for the first time that diazoxide-induced opening of mitoK_<ATP> channels triggers cardioprotection against apoptosis induced by oxidative stress in rat cardiomyocytes.
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Research Products
(2 results)