title: Propofol post-conditioning protects against cardiomyocyte apoptosis in hypoxia/reoxygenation injury by suppressing nuclear factor-kappa B translocation via extracellular signal-regulated kinase mitogen-activated protein kinase pathway.
abstract: OBJECTIVE
  Perioperative myocardial ischaemia leads to an exceedingly high mortality. Previous studies have indicated that propofol pre-conditioning could mimic the cardioprotective effects of ischaemic pre-conditioning. The purpose of this study was to determine whether propofol post-conditioning is cardioprotective and to explore the possible molecular mechanism of propofol post-conditioning.
  
  
  METHODS
  Primary cultured neonatal rat cardiomyocytes were exposed to 12 h of hypoxia followed by 4 h of reoxygenation (H/R) and post-conditioned by different concentrations of propofol at the onset of reperfusion with and without a specific inhibitor of extracellular signal-regulated kinases (ERKs). Cell apoptosis and the generation of intracellular reactive oxygen species were measured using FACScalibur flow cytometric analysis. ERK1/2 phosphorylation and nuclear factor-kappa B (NF-κB) translocation were determined by western blot and immunofluorescence, respectively.
  
  
  RESULTS
  Propofol post-conditioning enhanced cell viability (86.6 ± 6.5 versus 64.1 ± 3.4%) and reduced apoptosis (3.6 ± 0.4 versus 12.5 ± 2.1%) to protect cardiomyocytes against H/R injury. Meanwhile, propofol post-conditioning stimulated expression of phosphor-ERKs. H/R markedly induced p65 NF-κB nuclear translocation in cardiomyocytes, whereas propofol post-conditioning significantly suppressed H/R-primed NF-κB translocation. Moreover, addition of the mitogen-activated protein kinase kinase 1 inhibitor U0126 into cardiomyocytes 30 min before H/R eliminated the cardioprotection of propofol post-conditioning.
  
  
  CONCLUSIONS
  Propofol exerts cardioprotection when administered at the early phase of reperfusion. The effect is mediated through decrease in cardiomyocyte apoptosis and NF-κB nucleus translocation potentially via ERK signalling pathways.
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Tan
authors.forename: Zui
authors.initials: Z
authors.lastname: Zou
authors.forename: Cai-Guo
authors.initials: CG
authors.lastname: Huang
authors.forename: Xue-Yin
authors.initials: XY
authors.lastname: Shi
mesh_terms: D021581:Active Transport, Cell Nucleus; D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000196:embryology / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D015742:Propofol / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D018686:Anesthetics, Intravenous; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D015742:Propofol