ROLE OF APOPTOSIS ASSOCIATED WITH OXIDATIVE STRESS IN DIABETIC CARDIOMYOPATHY
| Project/Area Number |
14570681
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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 | OITA UNIVERSITY (FACULTY OF MEDICINE) |
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Principal Investigator |
YONEMOCHI Hidetoshi OITA UNIVERSITY, DEPARTMENT OF CARDIOVASCULAR SCIENCE, ASSOCIATED PROFESOR, 医学部, 助教授 (40191671)
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| Co-Investigator(Kenkyū-buntansha) |
OBATA Toshio OITA UNIVERSITY, DEPARTMENT OF PHARMACOLOGY AND THERAPEUTICS, RESEARCH ASSOCIATE, 医学部, 助手 (80169359)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | diabetes / apoptosis / reactive oxygen species / mitochondria / heart failure / ischemia / 酸化ストレス |
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| Research Abstract |
Diabetes and hyperglycemia are clear contributors to poor prognosis and the high incidence of cardiovascular diseases including heart failure, and these complications have become the major cause of morbidity and mortality in the diabetic population. Recent studies reported that the incidence of apoptosis increases in the hearts of patients with diabetes. However, the precise role and the cellular mechanism of apoptosis in heart failure associated with hyperglycemia and diabetes are not clear. We investigated whether hyperglycemia-Induced reactive oxygen species (ROS) production promotes apoptosis and enhances susceptibility to oxidative stress of neonatal rat cardiomyocytes. Flow cytometric analysis was performed as an assay system for apoptosis, ROS production and mitochondrial inner membrane potential (MitoP) using forward scatter (FSC), dichlorofluorescein and rhodamine-123, respectively.
Hyperglycemia exhibited dual effects on cell survival with time, either inhibiting or promoting
… More
apoptosis : hyperglycemia dose-dependently decreased rate of cells with low FSC signal within 72h, but inversely increased at 120h (75% and 170% of timed control at 25 mmol/L). However, hyperglycemia increased the susceptibility to H_20_2 of cells at 72h. Intracellular glutathione content decreased in cells with the increased susceptibility to H_20_2. Hyperglycemia caused a mild ROS production associated with hyperpolarized MitoP and subsequently a massive ROS production. Normalization of the mild ROS production by their scavengers abolished the observed anti-apoptotic effect and increased susceptibility. Inhibition of the massive ROS production attenuated pro-apoptotic action. Agents that alter mitochondrial metabolism such as 4-hydroxycyanocinnamic acid (4-OHCA) or thenoyltrifluoroacetone inhibited hyperglycemia-induced ROS production and MitoP hyperpolarization. 4-OHCA inhibited hyperglycemia-induced anti-apoptotic and enhanced susceptibility to H_20_2.
These results -demonstrated that hyperglycemia-induced ROS production is a cellular mechanism in coupling changes in glucose metabolism with regulation of myocardial apoptosis and tolerance to oxidative stress, and is at least in part responsible for diabetic cardiomyopathy. Less
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Report
(3 results)
Research Products
(3 results)
