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Inhibition of ROS-activated ERK1/2 pathway contributes to the protection of H2S against chemical hypoxia-induced injury in H9c2 cells

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Abstract

Hydrogen sulfide (H2S) has been shown to exert cardioprotective effects. However, the roles of extracellular signal-regulated protein kinases 1/2 (ERK1/2) in H2S-induced cardioprotection have not been completely elucidated. In this study, cobalt chloride (CoCl2), a chemical hypoxia mimetic agent, was applied to treat H9c2 cells to establish a chemical hypoxia-induced cardiomyocyte injury model. The results showed that pretreatment with NaHS (a donor of H2S) before exposure to CoCl2 attenuated the decreased cell viability, the increased apoptosis rate, the loss of mitochondrial membrane potential (ΔΨm), and the intracellular accumulation of reactive oxygen species (ROS) in H9c2 cells. Exposure of H9c2 cells to CoCl2 or hydrogen peroxide (H2O2) upregulated expression of phosphorylated (p) ERK1/2, which was reduced by pretreatment with NaHS or N-acetyl-l-cysteine, a ROS scavenger. More importantly, U0126, a selective inhibitor of ERK1/2, mimicked the above cytoprotection of H2S against CoCl2-induced injury in H9c2 cells. In conclusion, these results indicate that H2S protects H9c2 cells against chemical hypoxia-induced injury partially by inhibiting ROS-mediated activation of ERK1/2.

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Acknowledgments

The study was supported by Guangdong Science & Technology Planning Project (Nos. 2010B080701105, 2009B080701014, and 2007B080701030).

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Authors and Affiliations

  1. Department of Cardiovasology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Xiao-Bian Dong & Xin-Xue Liao

  2. Department of Hypertension and Vascular Diseases, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Xiao-Bian Dong & Xin-Xue Liao

  3. Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, People’s Republic of China

    Chun-Tao Yang

  4. Department of Cardiology, Huangpu Division of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Dong-Dan Zheng

  5. Department of Anesthesiology, Huangpu Division of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Li-Qiu Mo

  6. Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

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

  7. School of Nursing, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Mei-Fen Zhang

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  1. Xiao-Bian Dong
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Correspondence to Jian-Qiang Feng, Mei-Fen Zhang or Xin-Xue Liao.

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Xiao-Bian Dong and Chun-Tao Yang have contributed equally to this study.

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Dong, XB., Yang, CT., Zheng, DD. et al. Inhibition of ROS-activated ERK1/2 pathway contributes to the protection of H2S against chemical hypoxia-induced injury in H9c2 cells. Mol Cell Biochem 362, 149–157 (2012). https://doi.org/10.1007/s11010-011-1137-2

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  • DOI: https://doi.org/10.1007/s11010-011-1137-2

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