Heat shock transcription factor 1 attenuates TNFα-induced cardiomyocyte death through suppression of NFκB pathway.

Heat shock transcription factor 1 (HSF1), which has been identified as an endogenous cardioprotective factor, possesses potent anti-inflammatory effects. However, the underlying mechanisms have not been fully understood yet. In this study, we investigated the effects of HSF1-regulated RelA, a subunit of NFκB on cardiomyocyte death. Cultured cardiomyocytes were transfected with HSF1 plasmid before the treatment of TNFα. Cell death ratio was determined by cell staining. Additionally, the expression of RelA in the cytoplasm and cytonucleus as well as its subcellular location was detected, and the expression of heat shock proteins (HSP70 and HSP90) in the cardiomyocytes was also examined. Not only did TNFα remarkably enhanced cardiac cell death, but also elevated the expressions of intracellular RelA and elicited its translocation. Overexpression of HSF1 effectively attenuated cell death induced by TNFα. Although HSF1 didn't significantly inhibit the intracellular activation of RelA induced by TNFα at an early stage, HSF1 decreased the levels of RelA and the translocation of RelA in the cytoplasm and cell nucleus at late stage. Besides, the expression of HSP70 and HSP90 was significantly increased when HSF1 was overexpressed. These results suggested that HSF1 attenuated cardiomyocyte death via inhibiting activation of RelA as well as preventing its translocation from the cytoplasm to the cytonucleus, which was partially associated with HSP70 and HSP90 up-regulated by HSF1 overexpression.