title: Expression of human myoglobin in H9c2 cells enhances toxicity to added hydrogen peroxide.
abstract: Hydrogen peroxide (H2O2) is implicated in cardiac myocyte (CM) damage during myocardial ischemia-reperfusion (IR) injury. Myoglobin (Mb) is present in CM at significant concentrations and reacts with H2O2 to yield one- and two-electron oxidants that may promote myocardial injury. Paradoxically, hearts from mice lacking Mb are more susceptible to H2O2-induced dysfunction than the corresponding controls [U. Flogel, A. Godecke, L.O. Klotz, J. Schrader, Role of myoglobin in the anti-oxidant defense of the heart, FASEB J. 18 (2004) 1156-1158]. We have overexpressed wild-type or Y103F variant of human Mb in cultured CMs to test whether Mb protects against H2O2 insult. Contrary to expectation, cells expressing WT or the Y103F Mb show increased mitochondrial dysfunction and apoptosis, and decreased ATP in response to H2O2 that follows the order native < Y103F Mb < WT human Mb consistent with the increasing pro-oxidant activity for these proteins. These data indicate that (i) Mb promotes oxidative damage to cultured CM and (ii) Mb may be a useful target for the design of inhibitors of myocardial IR injury.
authors.affiliation: ANZAC Research Institute, Concord Hospital, Concord, NSW, Australia. pwitting@anzac.edu.au
authors.forename: Paul K
authors.initials: PK
authors.lastname: Witting
authors.forename: Wen-Qiang
authors.initials: WQ
authors.lastname: Liao
authors.lastname: Matthew J Harris
authors.forename: Jiri
authors.initials: J
authors.lastname: Neuzil
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D006418:Heme / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects; D009211:Myoglobin / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; D009211:Myoglobin; D017382:Reactive Oxygen Species; D014443:Tyrosine; D006418:Heme; D006861:Hydrogen Peroxide