Myocardial Ischemia and Cell Functions - Characterization of Free Radical-Induced Dysfunction of Sarcoplasmic Reticulum Calcium Transport and Excitation-Contraction Coupling System in Myocardium -
| Project/Area Number |
60571095
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
応用薬理学・医療系薬学
|
|---|
| Research Institution | Kanagawa Dental College |
|---|
Principal Investigator |
OKABE Eiichiro (1986) Kanagawa Dental College, 歯学部, 助教授 (50097276)
岡部 栄逸郎 (1985) 神奈川歯科大学, 歯学部, 講師
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HARA Akira Kanagawa Dental College, 歯学部, 助手
徳富 亘 神奈川歯科大学, 歯学部, 助手 (30147996)
TODOKI Kazuo Kanagawa Dental College, 歯学部, 助手 (90139577)
TOKUTOMI Wataru Kanagawa Dental College
|
|---|
| Project Period (FY) |
1985 – 1986
|
| Project Status |
Completed (Fiscal Year 1986)
|
| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1986: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1985: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
|---|
| Keywords | Free radical / Ischemia / Sarcoplasmic reticulum / Calcium / カルモジュリン |
|---|
| Research Abstract |
It has been demonstrated that the onset of myocardial ischemia is associated with a significant decrease in intracellular pH and proposed that breakdown of the excitation-contraction (E-C) coupling system plays a pivotal role in myocardial dysfunction during the course of acute ischemia. A breakdown of the E-C coupling system can explain the behavior of the ischemic muscle at a subcellular level. Recent studies suggest an involvement of free radicals in the pathophysiology of myocardial ischemia-induced cell damage. However, the extent of free radical involvement in the series of events leading to irreversible cell injury during the course of ischemia is unknown, and the mechanism of the effect of free radicals on function of sarcoplasmic reticulum (SR), the source and sink for coupling calcium in the E-C coupling system, requires clarification. In the present research project we consider the evidence supporting the hypothesis that hydroxyl radical, but not superoxide anion, is involved in a mechanism that may cause an increase in the calcium permeability of the SR membrane at pH 6.4, the intracelluar pH of the ischemic myocardium, and that the effect of hydroxyl radical is calmodulin dependent. There is also evidence that this breakdown in SR function may serve as the source of intracellular calcium overload. Thus it would appear that the generation of hydroxyl radical may represent a final pathway leading to tissue destruction in myocardial ischemia via SR dysfunction.
|
Report
(1 results)
Research Products
(12 results)
