title: Preventive role of propofol in hypoxia/reoxygenation-induced apoptotic H9c2 rat cardiac myoblast cell death.
abstract: Reperfusion of ischaemic myocardium is accompanied by cardiomyocyte apoptosis. Although a protective role of propofol in this process has been suggested, the exact mechanism of propofol activity remains to be elucidated. Here, we report that propofol protects cardiac H9c2 cells from hypoxia/reoxygenation-induced cell death by attenuating the phosphorylation of extracellular signal-regulated kinases (ERKs) and by up-regulating heme oxygenase 1 (HO-1) expression levels. Treatment with 25 µM propofol significantly protected against hypoxia/reoxygenation-induced cell death, as determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and Western blot analysis using anti-apoptotic signal proteins, such as apoptotic protease activating factor 1 and caspase 9. Propofol furthermore suppressed the ERK signaling pathway in cardiac H9c2 cells subjected to hypoxia/reoxygenation. The up-regulation of anti-oxidant enzymes such as HO-1, manganese superoxide dismutase (MnSOD) and catalase is also associated with the protective effect of propofol on hypoxia/reoxygenation-induced cell death. Taken together, the results reveal a new mechanism by which propofol inhibits hypoxia/reoxygenation-induced cell death in cardiac H9c2 cells, supporting a potential application of propofol as a preemptive cardioprotectant.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical Science and Engineering Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute (BK-21), School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Seonmin
authors.initials: S
authors.lastname: Lee
authors.forename: Kiyoon
authors.initials: K
authors.lastname: Kim
authors.forename: Yun Hong
authors.initials: YH
authors.lastname: Kim
authors.forename: Min Hyung
authors.initials: MH
authors.lastname: Chung
authors.forename: Insug
authors.initials: I
authors.lastname: Kang
authors.forename: Joohun
authors.initials: J
authors.lastname: Ha
authors.forename: Wonchae
authors.initials: W
authors.lastname: Choe
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D010100:Oxygen / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D051381:Rats
chemical_list: D000975:Antioxidants; D002316:Cardiotonic Agents; D048049:Extracellular Signal-Regulated MAP Kinases; D010100:Oxygen; D015742:Propofol