Effect of HSP70 on cardiomyocyte apoptosis induced by endoplasmic reticulum stress

We aimed to detect the role of HSP70 in endoplasmic reticulum (ER) stress-induced cell apoptosis, and to reveal the molecular mechanism underlying the HSP70 regulated ER stress induced-apoptosis, secretion and calcium signal transduction. The findings provide new intervention targets and theoretical basis of subcellular molecular application for myocardial protection. We used SD neonatal rat cardiomyocyte to establish a hypoxia cell model, and then we further detected the role of HSP70 in cell apoptosis, in production of ROS, in expression of casepase-12, CHOP, JNK pathway, CaSR and SERCA in ER caused by ER stress, as well as in the immunohistochemical staining of Bcl-xL, Bcl-2 and BAX, and Fas and FasL by overexpression or downexpression of HSP70. Results showed that 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 significantly inhibited the expression of Caspase-12, CaSR and CHOP. HSP70 increased the expression of JNK, but did not influent the expression of SERCA. HSP70 anti-sense oligonucleotide significantly increased the expression of CHOP, but did not significantly influent other tested molecules. Bcl-xL and Bcl-2 were highly expressed in HSP70-treated cells, but were low expressed in HSP70 anti-sense oligonucleotide-treated cells. Bax, Fas, FasL were predominantly expressed in cell treated with HSP70 anti-sense oligonucleotide, but were not in HSP70-treated cells. Thus, HSP70 inhibited the cell apoptosis via inhibiting the expression of Caspase 12, CHOP, Bax, Fas and FasL, and inhibited the Ca2+ current via inhibiting the expression of CaSR, and that the JNK pathway might play important roles in cell apoptosis and ROS-induced Ca2+ current.