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

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Abstract

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 H2O2, and the ROS generation, c-Jun N-terminal kinase (JNK) activity and apoptosis were examined. H2O2 significantly increased intracellular ROS generation and apoptotic cells as expected, and all these cellular events were greatly inhibited by overexpression of HSF1. However, H2O2-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 H2O2-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.

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Acknowledgments

We thank Mr. Guoping Zhang at Institutes of Biomedical Sciences, Fudan University, China for flow cytometry analysis and Dr. Issei Komuro at Chiba University Graduate School of Medicine, Japan for kindly providing the plasmids. This work was supported by National Natural Science Foundation of China (No. 30570741, No. 30871073 and No. 30930043).

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Authors and Affiliations

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

    Lei Zhang, Hong Jiang, Xiaoqing Gao, Yunzeng Zou, Ming Liu, Yanyan Liang, Ying Yu, Haozhu Chen & Junbo Ge

  2. Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China

    Yunzeng Zou, Haozhu Chen & Junbo Ge

  3. Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, 260-8670, Japan

    Weidong Zhu

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  1. Lei Zhang
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  2. Hong Jiang
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Correspondence to Hong Jiang or Yunzeng Zou.

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Lei Zhang, Hong Jiang, in order to and Xiaoqing Gao authors contributed equally to this work.

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Zhang, L., Jiang, H., Gao, X. et al. Heat shock transcription factor-1 inhibits H2O2-induced apoptosis via down-regulation of reactive oxygen species in cardiac myocytes. Mol Cell Biochem 347, 21–28 (2011). https://doi.org/10.1007/s11010-010-0608-1

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  • DOI: https://doi.org/10.1007/s11010-010-0608-1

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