title: Hypoxic preconditioning protects cardiomyocytes against hypoxia/reoxygenation injury through AMPK/eNOS/PGC-1α signaling pathway.
abstract: OBJECTIVE
  AMP-activated protein kinase (AMPK) is an important regulator of multiple cellular pathways in the setting of energetic stress. Whether AMPK plays a critical role in hypoxic preconditioning (HPC), protecting cardiomyocytes against hypoxia reoxygenation (H/R) injury remains uncertain.
  
  
  METHODS
  H9c2 cells were preconditioned by exposing to 10 min of hypoxia and 30 min of reoxygenation. Then, the preconditioned and non-preconditioned cardiomyocytes were exposed to 90 min of hypoxia followed by 120 min of reoxygenation.
  
  
  RESULTS
  HPC protected H9c2 cells against H/R injury, the AMPK inhibitor or eNOS inhibitor abolished the effect of HPC. Compared with H/R group, HPC significantly increased the expression of p-AMPK (Thr172). HPC also markedly increased p-eNOS (Ser1177) expression, which was abolished by AMPK inhibition. HPC significantly increased PGC-1α expression, which were nullified by AMPK inhibition or eNOS inhibition. HPC attenuated the oxidative stress by increasing the SOD activity and decreasing the MDA and ROS level, which were abolished by AMPK inhibition or eNOS inhibition. Interestingly, the AMPK activator metformin mimicked the effects of HPC in part.
  
  
  CONCLUSIONS
  These results indicated that HPC protects H9c2 cells against H/R injury by reducing oxidative stress partly via AMPK/eNOS/PGC-1α signaling pathway.
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing 210029, P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing 210029, P. R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing 210029, P. R. China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing 210029, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing 210029, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing 210029, P. R. China.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival; D005786:Gene Expression Regulation; D032383:Myocytes, Cardiac / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D017382:Reactive Oxygen Species; C015977:malealdehyde; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D013482:Superoxide Dismutase; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Hypoxia reoxygenation injury; hypoxic preconditioning; oxidative stress