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.

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.

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.

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.

Heat shock protein 70; Endoplasmic reticulum stress; Myocardial protection; Calmodulin; Calcium sensitive receptors; Apoptosis