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.

已经证明，心肌缺血的发作与细胞内pH值的显着降低相关，并提出激发 - 收缩（E-C）耦合系统的分解在急性缺血过程中心肌功能障碍中起关键作用。 E-C耦合系统的分解可以解释亚细胞水平的缺血性肌肉的行为。最近的研究表明，自由基参与心肌缺血诱导的细胞损伤的病理生理学。然而，在缺血过程中导致不可逆细胞损伤的一系列事件中自由基参与程度是未知的，并且自由基对肌浆网（SR）功能的影响的机理，需要澄清E-C辅助系统中钙的源源和下水道。在本研究项目中，我们考虑了支持的证据，证明羟基自由基（而不是超氧化阴离子）参与了一种机制，该机制可能会导致SR膜在pH 6.4（缺血性心肌的ellacelluar pH值）的钙渗透性提高，以及羟基自由基依赖素的效果。也有证据表明，SR功能中的这种分解可能是细胞内钙超负荷的来源。因此，看来羟基自由基的产生可能代表了通过SR功能障碍导致心肌缺血的组织破坏的最终途径。