Effects of heat shock protein 70 regulating endoplasmic reticulum calcium channel related protein on cardiomyocyte apoptosis

Abstract

Objective To observe the role of heat shock protein 70 (HSP70) in endoplasmic reticulum (ER) stress-induced cell apoptosis, and to investigate the molecular mechanism underlying the HSP70 regulating ER stress induced-apoptosis, secretion and calcium signal transduction. The fidings provide new intervention targets and theoretical basis of subcellular molecular application for myocardial protection. Methods We used SD neonatal rat cardiomyocytes to establish a hypoxia cell model, and then we further detected the role of HSP70 in cell apoptosis, production of reactive oxygen species (ROS), expression of calcium sensing receptor (CaSR) and sarco endoplasmic reticulum Ca2+ -ATPase (SERCA) 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 apoptosis rate [(28.60±1.83)%], ROS formation rate is 80.0%, HSP70 gene transfection group early apoptosis rate [(4.30±0.72)%], late apoptosis rate [(11.6±1.66)%], ROS formation rate is 38.5%, HSP70 treated with antisense oligonucleotides early apoptosis rate [(29.3±2.54)%], late apoptosis rate [(34.4±2.43)%], ROS formation rate of 77.0%, respectively, suggesting that HSP70 significantly inhibited the cell apoptosis and the production of ROS. The expression of CaSR in HSP70 gene transfection group was significantly lower than that in HSP70 antisense oligonucleotide group, but SERCA showed no significant difference, indicating that HSP70 significantly inhibited the expression of CaSR, but it had no influence on the expression of SERCA. Conclusion HSP70 inhibited the Ca2+ current via inhibiting the expression of CaSR, and the JNK pathway might play important roles in cell apoptosis and ROS-induced Ca2+ current. Key words: Heat shock protein 70; Endoplasmic reticulum stress; Myocardial protection; Calmodulin; Calcium sensitive receptors; Apoptosis