Heat shock protein 70 (HSP70) protects against cardiac diseases such as ischemia/reperfusion injury and myocardial infarction. However, the underlying mechanisms have not yet been fully characterized.Methods
In this study, we investigated the effects of reactive oxygen species (ROS) and transforming growth factor-β-activated kinase 1 (TAK1) on HSP70-regulated cardiomyocyte protection. Cultured cardiomyocytes of neonatal rats were transfected with HSP70, TAK1 or both of them before exposure to H2O2, and the ROS generation, p38 mitogen-activated protein kinase (p38) activity and apoptosis were examined.Results
H2O2 significantly enhanced intracellular ROS generation and apoptosis as expected, and all these cellular events were greatly abolished by overexpression of HSP70. However, H2O2-induced increments in p38 phosphorylation and cardiac cell apoptosis were largely enhanced by TAK1 overexpression, whereas the similar transfection did not affect the ROS generation in the cardiomyocytes. Moreover, inhibition of H2O2-increased ROS generation, p38 phosphorylation, and cardiomyocytes apoptosis by overexpression of HSP70 tended to disappear when the cells were cotransfected with TAK1.Conclusion
Our data suggest that HSP70 protects cardiomyocytes from apoptosis under oxidative stress through downregulation of intracellular ROS generation and inhibition of p38 phosphorylation. Although TAK1 itself has no effect on intracellular ROS accumulation, it may affect the inhibitory effects of HSP70 on ROS generation, p38 activity and cardiomyocyte injury.