Effects of transfected heat shock protein 70 on cysteinyl aspartate-specific protease-12, C/EBP homologous protein and c-Jun amino-terminal kinase signal pathway in endoplasmic reticulum stress

Abstract

Objective To study the effect of heat shock protein 70 (HSP70) on cysteinyl aspartate-specific protease (Caspase)-12, C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) signal pathway in the endoplasmic reticulum stress. Methods HSP70 gene was transfected into SD neonatal rat cardiomyocytes by lipofectin. We used SD neonatal rat cardiomyocytes to establish a hypoxia cell model, and then we further detected the role of HSP70 in cell apoptosis, in expression of Casepase-12, CHOP, JNK pathway in ER caused by ER stress, by overexpression or downexpression of HSP70. Results The early apoptosis rate of the blank group (9.28±0.83)%, late (28.60±1.83)%, HSP70 gene transfection group early apoptosis rate (4.30±0.72)%, late (11.6±1.66)%, HSP70 treated with antisense oligonucleotides early apoptosis rate (29.3±2.54)%, late (34.4±2.43)%. Hypoxia-induced cell apoptosis was inhibited by HSP70, but was promoted by HSP70 anti-sense oligonucleotide. Hypoxia-induced ROS production was also inhibited by HSP70, but was not inhibited by HSP70 anti-sense oligonucleotide. HSP70 signifiantly inhibited the expression of Caspase-12 and CHOP. HSP70 increased the expression of JNK. HSP70 anti-sense oligonucleotide significantly increased the expression of CHOP, but did not signifiantly inflent other tested molecules. Conclusion This study demonstrated that HSP70 reduce myocardial cell apoptosis by regulating the Caspase-12, C/EBP homologous protein and c-Jun aminoterminal kinase signal pathway of endoplasmic reticulum. Key words: Cardiomyocyte; Heat shock proteins 70; Endoplasmic reticulum stress; Cysteinyl aspartate-specific protease-12; C/EBP homologous protein; c-Jun N-terminal kinase; Apoptosis