从凋亡信号通路探讨热休克蛋白保护过氧化氢所致心肌细胞凋亡的机制  

Heat Shock Proteins Protect Cardiomyocytes against Apoptosis Induced by Hydrogen Peroxide through Interference with Two Signal Transduction Pathways

作　　者：肖卫民[1] 蒋碧梅[1] 石永忠[1] 刘梅冬[1] 唐道林[1] 夏珂[1] 王慷慨[1] 张华莉[1] 邓恭华[1] 肖献忠[1] 

机构地区：[1]中南大学湘雅医学院病理生理学教研室,湖南省长沙市410078

出　　处：《中国动脉硬化杂志》2003年第4期283-286,共4页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金 ( 3 0 0 0 0 0 69;3 0 2 70 5 3 3 );国家 973重点项目 (G2 0 0 0 0 5 690 8);教育部博士点专项基金 ( 2 0 0 2 0 5 3 3 0 3 2 )资助

摘　　要：为探讨热休克蛋白保护过氧化氢所致心肌细胞凋亡的分子机制 ,采用热休克对原代培养的新生大鼠心肌细胞进行预处理 ,以诱导热休克蛋白的表达 ,观察热休克蛋白对过氧化氢所致心肌细胞凋亡的保护作用。结果发现 ,热休克预处理导致心肌细胞热休克蛋白 70及αB 晶状体蛋白表达明显增加 ,同时显著抑制过氧化氢所致细胞色素C从线粒体释放 ,抑制Caspase 8、Caspase 9和Caspase 3活化及随后的心肌细胞凋亡。以上结果提示 ,热休克蛋白通过抑制线粒体信号通路与死亡受体通路的活化保护过氧化氢导致的心肌细胞凋亡 。Aim To explore the mechanisms that heat shock proteins protected cardiomyocytes against apoptosis induced by hydrogen peroxide (H 2O 2). Methods The expression of heat shock protein 70 and αB crystallin in neonatal rat cardiomyocytes were induced by heat shock response (42℃, 1 h, and recovery for different durations). Cardiomyocyte apoptosis induced by 0.5 mmol/L hydrogen peroxide (H 2O 2) was determined by flow cytometric analysis. The activities of caspase 3, caspase 8, caspase 9 were assayed by caspase colorimetric assay kit and Western blot. The release of cytochrome C from mitochondria was observed by isolation of cellular components and Western blot. Results The expression of HSP70 and αB crystallin in neonatal rat cardiomyocytes significantly increased at 3 h and reached peak at 6～12 h after heat shock response. Heat shock response could inhibite H 2O 2 induced release of cytochrome c from mitochondria to cytoplasm, activation of caspase 3, caspase 8, caspase 9, and subsequent apoptosis in cultured neonatal rat cardiomyocytes. Conclusions HSPs protected cardiomyocytes from apoptosis by inhibiting the activation of both mitochondrial and death receptor pathways.

关 键 词：病理生理学 心肌细胞内源性保护机制 Westem-blot 热休克蛋白 过氧化氢 细胞凋亡 线粒体信号通路 

分 类 号：R363[医药卫生—病理学]