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Myocardial Ischemia and Cell Functions - Characterization of Free Radical-Induced Dysfunction of Sarcoplasmic Reticulum Calcium Transport and Excitation-Contraction Coupling System in Myocardium -

心肌缺血和细胞功能 - 自由基诱导的心肌肌浆网钙转运和兴奋收缩耦合系统功能障碍的表征 -

基本信息

批准号：
60571095
负责人：
OKABE Eiichiro
金额：
$ 1.02万
依托单位：
Kanagawa Dental College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60571095/
关键词：
Free radical Ischemia Sarcoplasmic reticulum Calcium カルモジュリン

项目摘要

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.

研究表明，心肌缺血的发生与细胞内pH值的显著下降有关，并提出在急性缺血过程中，兴奋-收缩（E-C）偶联系统的破坏在心肌功能障碍中起关键作用。E-C偶联系统的破坏可以在亚细胞水平上解释缺血肌肉的行为。最近的研究表明自由基参与心肌缺血引起的细胞损伤的病理生理过程。然而，在缺血过程中，自由基在导致不可逆细胞损伤的一系列事件中的参与程度尚不清楚，自由基对肌浆网（SR）功能的影响机制需要澄清，SR是E-C偶联系统中偶联钙的来源和汇。在本研究项目中，我们考虑了支持以下假设的证据：在缺血心肌细胞内pH值为pH 6.4时，羟基自由基而非超氧阴离子参与了导致SR膜钙通透性增加的机制，并且羟基自由基的作用依赖于钙调素。也有证据表明，SR功能的破坏可能是细胞内钙超载的来源。因此，羟基自由基的产生可能是心肌缺血中通过SR功能障碍导致组织破坏的最终途径。