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.
出处
《中国动脉硬化杂志》
CAS
CSCD
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
