title: Heat stress induces apoptosis through transcription-independent p53-mediated mitochondrial pathways in human umbilical vein endothelial cell.
abstract: Cells apoptosis induced by intense heat stress is the prominent feature of heat-related illness. However, little is known about the biological effects of heat stress on cells apoptosis. Herein, we presented evidence that intense heat stress could induce early apoptosis of HUVEC cells through activating mitochondrial pathway with changes in mitochondrial membrane potential(ΔΨm), release of cytochrome c, and activation of caspase-9 and -3. We further revealed that p53 played a crucial role in heat stress-induced early apoptosis, with p53 protein rapidly translocated into mitochondria. Using pifithrin-α(PFT), a p53's mitochondrial translocation inhibitor, we found that pretreated with PFT, heat stress induced mitochondrial p53 translocation was significantly suppressed, accompanied by a significant alleviation in the loss of ΔΨm, cytochrome c release and caspase-9 activation. Furthermore, we also found that generation of reactive oxygen species (ROS) was a critical mediator in heat stress-induced apoptosis. In addition, the antioxidant MnTMPyP significantly decreased the heat stress-induced p53's mitochondrial translocation, followed by the loss of ΔΨm, cytochrome c release, caspase-9 activation and heat stress-mediated apoptosis. Conclusively, these findings indicate the contribution of the transcription-independent mitochondrial p53 pathway to early apoptosis in HUVEC cells induced by oxidative stress in response to intense heat stress.
authors.affiliation: 1] The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, P R China [2] Department of intensive care unit, General Hospital of Guangzhou Military Command, Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLA, Guangzhou, PR China [3].
authors.forename: Z T
authors.initials: ZT
authors.lastname: Gu
authors.affiliation: 1] Department of Oncology, Cancer Research Institute, Southern Medical University, Guangzhou, PR China [2].
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: 1] The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, P R China [2] Department of intensive care unit, General Hospital of Guangzhou Military Command, Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLA, Guangzhou, PR China [3].
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of intensive care unit, General Hospital of Guangzhou Military Command, Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLA, Guangzhou, PR China.
authors.forename: Y S
authors.initials: YS
authors.lastname: Liu
authors.affiliation: Department of Oncology, Cancer Research Institute, Southern Medical University, Guangzhou, PR China.
authors.forename: X B
authors.initials: XB
authors.lastname: Deng
authors.affiliation: Department of Oncology, Cancer Research Institute, Southern Medical University, Guangzhou, PR China.
authors.forename: S F
authors.initials: SF
authors.lastname: Huo
authors.affiliation: 1] The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, P R China [2] Department of intensive care unit, General Hospital of Guangzhou Military Command, Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLA, Guangzhou, PR China.
authors.forename: F F
authors.initials: FF
authors.lastname: Yuan
authors.affiliation: Department of intensive care unit, General Hospital of Guangzhou Military Command, Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLA, Guangzhou, PR China.
authors.forename: Z F
authors.initials: ZF
authors.lastname: Liu
authors.affiliation: Department of intensive care unit, General Hospital of Guangzhou Military Command, Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLA, Guangzhou, PR China.
authors.forename: H S
authors.initials: HS
authors.lastname: Tong
authors.affiliation: Department of intensive care unit, General Hospital of Guangzhou Military Command, Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLA, Guangzhou, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Su
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D020169:Caspases / Q000096:biosynthesis; D045304:Cytochromes c / Q000378:metabolism; D018869:Heat-Shock Response; D006358:Hot Temperature; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D045304:Cytochromes c; D020169:Caspases