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

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Abstract

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 H2O2. 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 H2O2 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.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (No. 30871073) and Science and Technology Commission of Shanghai Municipality (No. 09540703500). We thank Dr. Issei Komuro (Chiba University Graduate School of Medicine, Japan) for kindly providing HSF1 plasmids.

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Authors and Affiliations

  1. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, 200032, China

    Ying Yu, Ming Liu, Lei Zhang, Quan Cao, Peipei Zhang, Hong Jiang, Yunzeng Zou & Junbo Ge

  2. Institutes of Biomedical Science, Fudan University, Shanghai, China

    Yunzeng Zou & Junbo Ge

  3. Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai, China

    Junbo Ge

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  1. Ying Yu
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  2. Ming Liu
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  3. Lei Zhang
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  4. Quan Cao
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  5. Peipei Zhang
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  6. Hong Jiang
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  7. Yunzeng Zou
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  8. Junbo Ge
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Correspondence to Hong Jiang.

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Yu, Y., Liu, M., Zhang, L. et al. Heat shock transcription factor 1 inhibits H2O2-induced cardiomyocyte death through suppression of high-mobility group box 1. Mol Cell Biochem 364, 263–269 (2012). https://doi.org/10.1007/s11010-012-1226-x

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  • DOI: https://doi.org/10.1007/s11010-012-1226-x

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