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Exogenous hydrogen sulfide alleviates high glucose-induced cardiotoxicity via inhibition of leptin signaling in H9c2 cells

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Abstract

Hydrogen sulfide (H2S) protects cardiomyoblasts against high glucose (HG)-induced injury by inhibiting the activation of p38 mitogen-activated protein kinase (MAPK). This study aims to determine whether the leptin–p38 MAPK pathway is involved in HG-induced injury and whether exogenous H2S prevents the HG-induced insult through inhibition of the leptin–p38 MAPK pathway in H9c2 cells. H9c2 cells were treated with 35 mM glucose (HG) for 24 h to establish a HG-induced cardiomyocyte injury model. Cell viability; mitochondrial membrane potential (ΔΨ m); apoptosis; reactive oxygen species (ROS) level; and leptin, leptin receptor, and p38 MAPK expression level were measured by the methods indicated. The results showed pretreatment of H9c2 cells with NaHS before exposure to HG led to an increase in cell viability, decrease in apoptotic cells, ROS generation, and a loss of ΔΨ m. Exposure of H9c2 cells to 35 mM glucose for 24 h significantly upregulated the expression levels of leptin and leptin receptors. The increased expression levels of leptin and leptin receptors were markedly attenuated by pretreatment with 400 μM NaHS. In addition, the HG-induced increase in phosphorylated (p) p38 MAPK expression was ameliorated by pretreatment with 50 ng/ml leptin antagonist. In conclusion, the present study has demonstrated for the first time that the leptin–p38 MAPK pathway contributes to the HG-induced injury in H9c2 cells and that exogenous H2S protects H9c2 cells against HG-induced injury at least in part by inhibiting the activation of leptin–p38 MAPK pathway.

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Acknowledgments

This study was supported by the National Nature Science Foundation of China (No. 81270296) and Science and Technology Planning Project of Guangdong Province in China (2010B080701105 and 2010B080701044).

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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-Dong Zhuang, Xun Hu, Ming Long, 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

    Xin-Xue Liao

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

    Dong-Hong Liu

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  1. Xiao-Dong Zhuang
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  2. Xun Hu
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  3. Ming Long
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  4. Xiao-Bian Dong
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Correspondence to Dong-Hong Liu or Xin-Xue Liao.

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Xiao-Dong Zhuang and Xun Hu have contributed equally to this work.

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Zhuang, XD., Hu, X., Long, M. et al. Exogenous hydrogen sulfide alleviates high glucose-induced cardiotoxicity via inhibition of leptin signaling in H9c2 cells. Mol Cell Biochem 391, 147–155 (2014). https://doi.org/10.1007/s11010-014-1997-3

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  • DOI: https://doi.org/10.1007/s11010-014-1997-3

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