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Hydrogen sulfide protects H9c2 cells against doxorubicin-induced cardiotoxicity through inhibition of endoplasmic reticulum stress

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Abstract

The roles of hydrogen sulfide (H2S) and endoplasmic reticulum (ER) stress in doxorubicin (DOX)-induced cardiotoxicity are still unclear. This study aimed to dissect the hypothesis that H2S could protect H9c2 cells against DOX-induced cardiotoxicity by inhibiting ER stress. Our results showed that exposure of H9c2 cells to DOX significantly inhibited the expression and activity of cystathionine-γ-lyase (CSE), a synthetase of H2S, accompanied by the decreased cell viability and the increased reactive oxygen species (ROS) accumulation. In addition, exposure of cells to H2O2 (an exogenous ROS) mimicked the inhibitory effect of DOX on the expression and activity of CSE. Pretreatment with N-acetyl-l-cysteine (NAC) (a ROS scavenger) attenuated intracellular ROS accumulation, cytotoxicity, and the inhibition of expression and activity of CSE induced by DOX. Notably, the ER stress-related proteins, including glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) were obviously upregulated in DOX-treated H9c2 cells. Pretreatment with sodium hydrosulfide (NaHS, a H2S donor) before DOX exposure markedly suppressed DOX-induced overexpressions of GRP78 and CHOP, cytotoxicity and oxidative stress. In conclusion, we have demonstrated that ROS-mediated inhibition of CSE is involved in DOX-induced cytotoxicity in H9c2 cells, and that exogenous H2S can confer protection against DOX-induced cardiotoxicity partly through inhibition of ER stress.

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Acknowledgments

This study was supported by Science and Technology Planning Project of Guangdong Province in China (2010B080701035, 2009B080701014, and 2007B080701030).

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Authors and Affiliations

  1. Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China

    Xiu-Yu Wang, Ai-Ping Lan, Zhan-Li Yang, Fen Hu, Pei-Xi Chen & Jian-Qiang Feng

  2. Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, China

    Chun-Tao Yang

  3. Department of Cardiology, Huangpu Division of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Dong-Dan Zheng

  4. Department of Anesthesiology, Huangpu Division of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Li-Qiu Mo

  5. Department of Cardiovasology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Xin-Xue Liao

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  1. Xiu-Yu Wang
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  2. Chun-Tao Yang
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  7. Fen Hu
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  9. Xin-Xue Liao
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Corresponding authors

Correspondence to Xin-Xue Liao or Jian-Qiang Feng.

Additional information

X.-Y. Wang and C.-T. Yang contributed equally to this study.

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Wang, XY., Yang, CT., Zheng, DD. et al. Hydrogen sulfide protects H9c2 cells against doxorubicin-induced cardiotoxicity through inhibition of endoplasmic reticulum stress. Mol Cell Biochem 363, 419–426 (2012). https://doi.org/10.1007/s11010-011-1194-6

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  • DOI: https://doi.org/10.1007/s11010-011-1194-6

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