Reactive oxygen species mediate heat stress-induced apoptosis via ERK dephosphorylation and Bcl-2 ubiquitination in human umbilical vein endothelial cells

  • Li L
  • Tan H
  • Yang H
  • et al.
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Abstract

Heat stress can induce the mitochondrial apoptotic pathway in HUVEC cells, indicating that apoptosis may be a prominent pathological feature of heat stroke, however, little is known about the precise mechani sms involved in it. In this study, we describe the apoptotic effect of intense heat stress on HUVEC cells and our investigation of its underlying mechanisms. Treatment of cells with intense heat stress induced production of reactive oxygen species (ROS) and a concomitant increase in activation of the mitochondrial apoptotic pathway. Furthermore, by over-expression of MnSOD and GPx in cells, we show that ROS, and especially superoxide, is the primary oxidative species induced by intense heat stress and responsible for cell death. In addition, we explored the mechanism by which superoxide regulates the apoptotic effect of intense heat stress, and found that it involved Bcl-2 down-regulation through ubiquitin - proteasomal degradation. Superoxide production also led to Bcl-2 dephosphorylation through inactivation of MAP kinase ERK1/2, which promoted Bcl-2 ubiquitination. Taken together, these findings describe a novel pathway downstream of heat stress-induced apoptosis in HUVEC cells, and provide new insight into the process of redox-mediated down-regulation of Bcl-2 and apoptosis induction. These results could be important in the understanding of pathogenesis of heat stroke and for the development of preventive and treatment measures, both of which are currently lacking.

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Li, L., Tan, H., Yang, H., Li, F., He, X., Gu, Z., … Su, L. (2016). Reactive oxygen species mediate heat stress-induced apoptosis via ERK dephosphorylation and Bcl-2 ubiquitination in human umbilical vein endothelial cells. Oncotarget, 8(8). https://doi.org/10.18632/oncotarget.14186

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