Induction of HSP 32 gene in hypoxic cardiomyocytes is attenuated by treatment with N-acetyl-L-cysteine.
Increased synthesis of stress proteins may enhance myocardial viability during periods of low oxygen delivery. Our purpose was to determine if the oxidative stress protein heme oxygenase-1 [heat stress protein 32 (HSP 32)] was induced in hypoxic cardiomyocytes and whether this induction might be mediated by a redox-sensitive mechanism. Primary rat neonatal cardiomyocytes, cultured to express a tissuelike phenotype, responded to 12 h of hypoxia (< 0.5% ambient oxygen) with an approximately fivefold (range 3- to 7.5-fold; P < 0.05) increase in HSP 32 mRNA and a threefold (P < 0.05) increase in HSP 32 protein content. Exposure to 80 microM H2O2 for 3 h increased HSP 32 mRNA content to a similar extent. Expression of heme oxygenase-2 mRNA was unaffected by H2O2 or hypoxic treatments. Inclusion of 20 mM N-acetyl-L-cysteine in the medium during hypoxia reduced the increase in HSP 32 mRNA and protein expression by 25.50% compared with hypoxia alone. The data suggest that induction of HSP 32 protein may lead to an improved antioxidant defense in cardiomyocytes during hypoxia and that a redox-sensitive pathway mediates at least a portion of the hypoxic induction of the HSP 32 gene.
Borger
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DR
Department of Exercise Science, University of South Carolina, Columbia 29208, USA.
Essig
D A
DA
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D000860:Hypoxia / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010105:Oxygenases; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D006360:Heat-Shock Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D000111:Acetylcysteine