Ischemia-reperfusion alters gene expression of Na super(+)-K super(+) ATPase isoforms in rat heart

The present study investigated whether oxidative stress plays a role in ischemia-reperfusion-induced changes in cardiac gene expression of Na super(+)-K super(+) ATPase isoforms. The levels of mRNA for Na super(+)-K super(+) ATPase isoforms were assessed in the isolated rat heart subjected to global ischemia (30min) followed by reperfusion (60min) in the presence or absence of superoxide dismutase (510 super(4)U/L) plus catalase (7.510 super(4)U/L), an antioxidant mixture. The levels of mRNA for the alpha 2, alpha 3, and beta 1 isoforms of Na super(+)-K super(+) ATPase were significantly reduced in the ischemia-reperfusion hearts, unlike the alpha 1 isoform. Pretreatment with superoxide dismutase+catalase preserved the ischemia-reperfusion-induced changes in alpha 2, alpha 3, and beta 1 isoform mRNA levels of the Na super(+)-K super(+) ATPase, whereas the alpha 1 mRNA levels were unaffected. In order to test if oxidative stress produced effects similar to those seen with ischemia-reperfusion, hearts were perfused with an oxidant, H2O2 (300 mu M), or a free radical generator, xanthine (2mM) plus xanthine oxidase (0.03U/ml) for 20min. Perfusion of hearts with H2O2 or xanthine/xanthine oxidase depressed the alpha 2, alpha 3, and beta 1 isoform mRNA levels of the Na super(+)-K super(+) ATPase, but had lesser effects on alpha 1 mRNA levels. These results indicate that Na super(+)-K super(+) ATPase isoform gene expression is altered differentially in the ischemia-reperfusion hearts and that antioxidant treatment appears to attenuate these changes. It is suggested that alterations in Na super(+)-K super(+) ATPase isoform gene expression by ischemia-reperfusion may be mediated by oxidative stress.