Heat shock transcription factor 1 inhibits H₂O₂-induced cardiomyocyte death through suppression of high-mobility group box 1.

Heat shock transcription factor 1 (HSF1), which has been identified as an endogenous cardioprotective factor, possesses considerable anti-inflammatory effects and the ability against oxidative stress. However, the mechanisms have not been fully characterized yet. In this study, we investigated the effects of HSF1-regulated HMGB1 on cardiomyocyte death. Cultured cardiomyocytes were transfected with empty vector or HSF1 plasmid before the exposure to H(2)O(2). Cell death was assessed by cell staining. Additionally, the levels of intracellular and extracellular HMGB1 as well as its subcellular location were detected, and the expression of heat shock proteins (HSP27 and HSP90) in the cardiomyocytes was also determined. Not only did H(2)O(2) significantly increase cell death, but also elevated the levels of intracellular and extracellular HMGB1 and induced its translocation, whereas, as expected, HSF1 overexpression effectively attenuated cell death. Furthermore, HSF1 inhibited the intracellular expression of HMGB1 at early stage of oxidative stress and subsequently, HSF1 did negatively regulate the extracellular levels and the translocation of HMGB1 at late stage. Besides, the expression of HSP27 and HSP90 was significantly increased. These results suggested HSF1-attenuated cardiomyocyte death via reducing intracellular and extracellular levels of HMGB1 as well as preventing its translocation, which was partially associated with HSP27 and HSP90 up-regulated by HSF1 overexpression.