Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Mol Cell Biochem. 2012 May;364(1-2):263-9. doi: 10.1007/s11010-012-1226-x. Epub 2012 Jan 15.
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.
热休克转录因子 1（HSF1）已被确定为一种内源性心脏保护因子，具有相当强的抗炎作用和抗氧化应激能力。然而，其机制尚未完全阐明。在本研究中，我们研究了 HSF1 调节的高迁移率族蛋白 B1（HMGB1）对心肌细胞死亡的影响。在暴露于 H2O2 之前，用空载体或 HSF1 质粒转染培养的心肌细胞。通过细胞染色评估细胞死亡。此外，还检测了细胞内和细胞外 HMGB1 的水平及其亚细胞定位，并测定了心肌细胞中热休克蛋白（HSP27 和 HSP90）的表达。H2O2 不仅显著增加了细胞死亡，还增加了细胞内和细胞外 HMGB1 的水平，并诱导其易位，而 HSF1 的过表达如预期的那样有效地减轻了细胞死亡。此外，HSF1 在氧化应激的早期阶段抑制了细胞内 HMGB1 的表达，随后，HSF1 在晚期阶段负调控了细胞外水平和 HMGB1 的易位。此外，HSP27 和 HSP90 的表达显著增加。这些结果表明，HSF1 通过降低细胞内和细胞外 HMGB1 的水平以及防止其易位来减轻心肌细胞死亡，这部分与 HSF1 过表达上调的 HSP27 和 HSP90 有关。
