Heat shock transcription factor-1 inhibits H2O2-induced apoptosis via down-regulation of reactive oxygen species in cardiac myocytes.

Heat shock transcription factor-1 (HSF1) protects against cardiac diseases such as ischemia/reperfusion injury and myocardial infarction. However, the mechanisms have not yet been fully characterized. In this study, we investigated the effects of reactive oxygen species (ROS) and apoptosis signal-regulating kinase-1 (ASK1) in HSF1-regulated cardiomyocyte protection. Cultured cardiomyocytes of neonatal rats were transfected with HSF1, ASK1 or both of them before exposure to H(2)O(2), and the ROS generation, c-Jun N-terminal kinase (JNK) activity and apoptosis were examined. H(2)O(2) significantly increased intracellular ROS generation and apoptotic cells as expected, and all these cellular events were greatly inhibited by overexpression of HSF1. However, H(2)O(2)-induced increases in JNK phosphorylation and cell apoptosis were largely enhanced by ASK1 overexpression whereas the similar transfection did not affect the ROS generation in the cells. Moreover, inhibition of H(2)O(2)-increased ROS generation, JNK phosphorylation, and cellular apoptosis by overexpression of HSF1 tended to be disappeared, when the cells were co-transfected with ASK1. These results suggest that HSF1 protects cardiomyocytes from apoptosis under oxidative stress via down-regulation of intracellular ROS generation and inhibition of JNK phosphorylation. Although ASK1 itself has no effect on intracellular ROS generation, it may affect the inhibitory effects of HSF1 on ROS generation, JNK activity, and cardiomyocyte injury.