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 viabilit y 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 in duction might be mediated by a redox-sensitive mechanism. Primary rat neonatal cardiomyocytes, cultured to express a tissuelike phenotype, r esponded to 12 h of hypoxia (<0.5% ambient oxygen) with an approximate ly fivefold (range 3- to 7.5-fold; P < 0.05) increase in HSP 32 mRNA a nd a threefold (P < 0.05) increase in HSP 32 protein content. Exposure to 80 mu M H2O2 for 3 h increased HSP 32 mRNA content to a similar ex tent. Expression of heme oxygenase-2 mRNA was unaffected by H2O2 or hy poxic treatments. Inclusion of 20 mM N-acetyl-L-cysteine in the medium during hypoxia reduced the increase in HSP 32 mRNA and protein expres sion by 25-50% compared with hypoxia alone. The data suggest that indu ction of HSP 32 protein may lead to an improved antioxidant defense in cardiomyocytes during hypoxia and that a redox-sensitive pathway medi ates at least a portion of the hypoxic induction of the HSP 32 gene.