, Volume 64, Issue 1, pp 65–73 | Cite as

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

  • Zhilong Chen
  • Hong Jiang
  • Yanwu Wan
  • Chaofang Bi
  • Yian Yuan
Original Research


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.


p38 mitogen-activated protein kinases Tumor necrosis factor-α Reactive oxygen species Apoptosis 



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

Conflict of interest

The authors state no conflict of interest.


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Zhilong Chen
    • 1
  • Hong Jiang
    • 1
  • Yanwu Wan
    • 2
  • Chaofang Bi
    • 2
  • Yian Yuan
    • 2
  1. 1.Department of CardiologyRenmin Hospital of Wuhan UniversityWuhanChina
  2. 2.Huangshi Central HospitalHuangshiChina

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