title: Heat stress induced apoptosis is triggered by transcription-independent p53, Ca(2+) dyshomeostasis and the subsequent Bax mitochondrial translocation.
abstract: In 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Department of intensive care unit, The Third Affiliated Hospital of Southern Medical University, Guangzhou, P.R. China; Department of Pathophysiology, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Z T
authors.initials: ZT
authors.lastname: Gu
authors.affiliation: Department of intensive care unit, The Third Affiliated Hospital of Southern Medical University, Guangzhou, P.R. China; Department of Pathophysiology, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Southern Medical University, Guangzhou, P.R. China.
authors.forename: F
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Gerontology, 421 Hospital of PLA, P.R. China.
authors.forename: P
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of intensive care unit, The Third Affiliated Hospital of Southern Medical University, Guangzhou, P.R. China; Department of Pathophysiology, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of intensive care unit, General Hospital of Guangzhou Military Command, Key Laboratory of Tropical Zone Trauma treatment and Tissue Repair of PLA, Guangzhou, PR China.
authors.forename: Y S
authors.initials: YS
authors.lastname: Liu
authors.affiliation: Department of intensive care unit, General Hospital of Guangzhou Military Command, Key Laboratory of Tropical Zone Trauma treatment and Tissue Repair of PLA, Guangzhou, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Department of Pathophysiology, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of intensive care unit, General Hospital of Guangzhou Military Command, Key Laboratory of Tropical Zone Trauma treatment and Tissue Repair of PLA, Guangzhou, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Su
mesh_terms: D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death; D002470:Cell Survival; D018869:Heat-Shock Response / Q000235:genetics*; D006706:Homeostasis; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D002118:Calcium