Heat stress induced apoptosis is triggered by transcription-independent p53, Ca2+ dyshomeostasis and the subsequent Bax mitochondrial translocation

• DOI: 10.1038/srep11497
• Publication Date: 2015-06-24T09:17:24Z
• Authors: Z. T. Gu; L. Li; F. WU; P. Zhao; H. Yang; Y. S. Liu; Y. Geng; M. Zhao; L. Su
• Keywords: 0303 health sciences; Cell Death; Transcription, Genetic; Cell Survival; Mitochondrial Permeability Transition Pore; Apoptosis; Mitochondrial Membrane Transport Proteins; Article; Mitochondria; Protein Transport; 03 medical and health sciences; Human Umbilical Vein Endothelial Cells; Homeostasis; Humans; Calcium; Tumor Suppressor Protein p53; Reactive Oxygen Species; Heat-Shock Response; Signal Transduction; bcl-2-Associated X Protein

AbstractIn this study, We demonstrated that Bax mitochondrial translocation plays a vital role in the initiation of the mitochondrial signaling pathway upon activation by heat stress. In addition, both p53 mitochondrial translocation and Ca2+ signal mediated MPTP opening activate Bax mitochondrial translocation. Employing pifithrin-α (a p53 mitochondrial translocation inhibitor) and CsA (a permeability transition pore (MPTP) inhibitor), we found that heat stress induced Bax mitochondrial translocation was significantly inhibited in cells pretreated with both PFT and CsA. Furthermore, we demonstrated that generation of reactive oxygen species (ROS) is a critical mediator in heat stress induced apoptosis and that the antioxidant MnTBAP significantly decreased heat stress induced p53 mitochondrial translocation and Ca2+ signal mediated MPTP opening, as well as the subsequent Bax mitochondrial translocation and activation of the caspase cascade. Taken together, our results indicate that heat stress induces apoptosis through the mitochondrial pathway with ROS dependent mitochondrial p53 translocation and Ca2+ dyshomeostasis and the ensuing intro Bax mitochondrial translocation as the upstream events involved in triggering the apoptotic process observed upon cellular exposure to heat stress.