title: Oxygen glucose deprivation (OGD)/re-oxygenation-induced in vitro neuronal cell death involves mitochondrial cyclophilin-D/P53 signaling axis.
abstract: Oxidative stress-induced neuronal cell death requires opening of the mitochondrial permeability transition pore. P53 mitochondrial translocation and association with Cyclophilin D (Cyp-D) is required for the pore opening. Here we tested this signaling axis in oxygen glucose deprivation (OGD)/re-oxygenation-induced in vitro neuronal death. Using mitochondrion immunoprecipitation, we found that p53 translocated to mitochondrion and associated with Cyp-D in SH-SY5Y cells exposed to (OGD)/re-oxygenation. Disruption of this complex by Cyp-D inhibitor Cyclosporine A (CsA), or by Cyp-D or p53 deficiency, significantly inhibited OGD/re-oxygenation-induced apoptosis-independent cell death. Conversely, over-expression of Cyp-D in SH-SY5Y cells caused spontaneous cell death, and these cells were more vulnerable to OGD/re-oxygenation. Finally, CsA or Cyp-D RNAi suppressed OGD/re-oxygenation-induced neuronal cell death in primary cultures. Together, our study suggests that OGD/re-oxygenation-induced in vitro cell death involves a mitochondrial Cyp-D/p53 signaling axis.
authors: State Key Laboratory of Reproductive Medicine, Department of Anesthesiology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
authors: Li-Ping
authors: LP
authors: Zhao
authors: Chao
authors: C
authors: Ji
authors: Pei-Hua
authors: PH
authors: Lu
authors: Chen
authors: C
authors: Li
authors: Bo
authors: B
authors: Xu
authors: Hong
authors: H
authors: Gao
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D051379:Mice; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D009474:Neurons / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000502:physiology*
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C000631446:PPIF protein, mouse; D016159:Tumor Suppressor Protein p53; D016572:Cyclosporine; D021983:Cyclophilins; D010100:Oxygen