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Oxygen radical-induced tissue injury

氧自由基引起的组织损伤

基本信息

批准号：
02557090
负责人：
KUDO Ichiro
金额：
$ 8.9万
依托单位：
UNIVERSITY OF TOKYO
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

Phospholipid-hydrolyzing activities were examined in rat hearts with ischemia induced by occlusion of the left main coronary artery. When homogenates of ischemic heart were incubated in vitro at 37 ﾟC, a significant amount of phosphatidylethanolamine (PE) was degraded, whereas the contents of other phospholipids did not change significantly. During the incubation, a stoichiometrical amount of lysoPE bearing mainly saturated fatty acids, whose composition resembled that of fatty acids detected at the sn-1 position in the glycerol backbone of heart PE, was formed concomitantly. No appreciable PE degradation was observed in homogenates prepared from nonischemic heart. No difference in phospholipase activities was found between ischemic and nonischemic heart homogenates when exogenous radioactive phospholipids were used as substrates. Anti-rat type II phospholipase A_2(PLA_2) antibody suppressed the degradation of PE observed in ischemic heart homogenates. These findings indicate that type II PLA_2 activity may be involved in the breakdown of endogenous PE in ischemic heart homogenates.Activation of type II PLA_2, leading to hydrolysis of endogenous PE, was also observed in other oxygen radical-induced tissue injury, such as CCl_4-treated rat liver. Certain lipid-derived compound(s), which activated type II PLA_2, were detected in homogenate of CCl_4-treated liver. In the presence of lipids derived from CCl_4-treated liver, type II PLA_2 was significantly activated at lower (10^<-6> to 10^<-5> M) Ca^<2+> concentrations. Production of peroxidized lipids might explain the progressed breakdown of endogenous PE by type II PLA_2 in oxygen-injured tissues.

在左主冠状动脉闭塞引起缺血的大鼠心脏中检查磷脂水解活性。缺血心脏匀浆在37℃体外培养时，磷脂酰乙醇胺（PE）大量降解，而其他磷脂含量没有明显变化。在孵育过程中，同时形成了主要含有饱和脂肪酸的化学计量的溶血PE，其组成与在心脏PE的甘油主链中的sn-1位置处检测到的脂肪酸的组成相似。在由非缺血心脏制备的匀浆中没有观察到明显的 PE 降解。当使用外源放射性磷脂作为底物时，缺血性和非缺血性心脏匀浆之间的磷脂酶活性没有差异。抗大鼠 II 型磷脂酶 A_2(PLA_2) 抗体抑制缺血心脏匀浆中观察到的 PE 降解。这些发现表明II型PLA_2活性可能参与缺血心脏匀浆中内源性PE的分解。II型PLA_2的激活导致内源性PE水解，在其他氧自由基诱导的组织损伤中也观察到，例如CCl_4处理的大鼠肝脏。在 CCl_4 处理的肝脏匀浆中检测到某些激活 II 型 PLA_2 的脂质衍生化合物。在存在源自CCl_4处理的肝脏的脂质的情况下，II型PLA_2在较低(10 ^ -6 至10 ^ -5 M)Ca 2+ 浓度下被显着激活。过氧化脂质的产生可能解释了氧损伤组织中 II 型 PLA_2 对内源性 PE 的逐渐分解。