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H2O2-induced secretion of tumor necrosis factor-α evokes apoptosis of cardiac myocytes through reactive oxygen species-dependent activation of p38 MAPK

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Abstract

P38 mitogen-activated protein kinases (p38 MAPK) and tumor necrosis factor-α (TNF-α) play important roles in oxidative stress-induced apoptosis in cardiac myocytes. However, the regulation and functional role of cross-talk between p38 MAPK and TNF-α pathways have not yet been fully characterized in cardiac myocytes. In this study, we found that inhibition of p38 MAPK with SB-203580 (SB) reduced H2O2-stimulated secretion of TNF-α, whereas pre-activation of p38 MAPK with sodium arsenite (SA) enhanced H2O2-stimulated secretion of TNF-α. In addition, pretreatment of cells with TNF-α increased basal and H2O2-stimulated p38 MAPK and apoptosis of cardiac myocytes, and p38 MAPK-associated apoptosis of cardiac myocytes induced by TNF-α was blocked by inhibition of p38 MAPK with SB. Finally, H2O2-induced apoptosis was attenuated by the inhibitors of p38 MAPK or reactive oxygen species (ROS), whereas it was enhanced by p38 MAPK agonist SA. These results suggest that H2O2-induced secretion of TNF-α increases apoptosis of cardiac myocytes through ROS-dependent activation of p38 MAPK. This may represent a novel mechanism that TNF-α partly interplays with p38 MAPK pathways during oxidative stress-modulated apoptosis in cardiac myocytes.

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Acknowledgments

We thank Dr Chen for his excellent technical assistance. This work was supported by the grant from Natural Science fund of Hubei Province (2009CDB244).

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The authors state no conflict of interest.

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Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, 99 Zi Yang Road, Wuhan, 430060, Hubei, China

    Zhilong Chen & Hong Jiang

  2. Huangshi Central Hospital, Huangshi, 435000, Hubei, China

    Yanwu Wan, Chaofang Bi & Yian Yuan

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  1. Zhilong Chen
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  2. Hong Jiang
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  3. Yanwu Wan
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  4. Chaofang Bi
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  5. Yian Yuan
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Correspondence to Hong Jiang.

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Chen, Z., Jiang, H., Wan, Y. et al. H2O2-induced secretion of tumor necrosis factor-α evokes apoptosis of cardiac myocytes through reactive oxygen species-dependent activation of p38 MAPK. Cytotechnology 64, 65–73 (2012). https://doi.org/10.1007/s10616-011-9392-3

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  • DOI: https://doi.org/10.1007/s10616-011-9392-3

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