title: PINK1 alleviates myocardial hypoxia-reoxygenation injury by ameliorating mitochondrial dysfunction.
abstract: PTEN inducible kinase-1 (PINK1) mutant induces mitochondrial dysfunction of cells, resulting in an inherited form of Parkinson's disease. However its exact role in the cardiomyocytes is unclear. The present study examined the function of PINK1 in hypoxia-reoxygenation (H/R) induced H9c2 cell damage and its potential mechanism. The H/R model in H9c2 cells was established by 6 h of hypoxia and 12 h of reoxygenation. The CCK8 and LDH assay indicated that the cell viability was obviously reduced after H/R. The expression of PINK1 was decreased in H/R-induced H9c2 cells compared with control group. The vector overexpressing PINK1 was constructed to transfect into H/R-induced H9c2 cells. Our results showed that cell viability was increased, cell apoptosis and caspase 3, cytochrome C (Cyto C) levels were decreased after LV-PINK1 transfection. Furthermore, PINK1 overexpression stabilized electron transport chain (ETC) activity, increased ATP production, mPTP opening and mitochondrial membrane potential (MMP), inhibited ROS-generating mitochondria, implying PINK1 alleviates H/R induced mitochondrial dysfunction in cardiomyocytes. In addition, the TRAP-1 siRNA was transfected into PINK1 treated H9c2 cells after H/R to detected the molecular mechanism of PINK1 protecting cardiomyocytes. The results indicated that silence of TRAP-1 reversed the effects of PINK1 in H/R-induced H9c2 cells. In conclusion, these results suggest that PINK1 overexpression alleviates H/R-induced cell damage of H9c2 cells by phosphorylation of TRAP-1, and that is a valid approach for protection from myocardial I/R injury.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, PR China.
authors.forename: Liangxian
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, PR China.
authors.forename: Xiping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, PR China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Hou
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, PR China. Electronic address: boyubuy@sina.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D008929:Mitochondria, Heart / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D000099202:PTEN-Induced Putative Kinase
chemical_list: D018841:HSP90 Heat-Shock Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010100:Oxygen; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase; C549284:TRAP1 protein, rat
keywords: Cardiomyocytes; Hypoxia-reoxygenation; PINK1; TRAP-1