title: Ischemia-reperfusion alters gene expression of Na+-K+ ATPase isoforms in rat heart.
abstract: The present study investigated whether oxidative stress plays a role in ischemia-reperfusion-induced changes in cardiac gene expression of Na(+)-K(+) ATPase isoforms. The levels of mRNA for Na(+)-K(+) ATPase isoforms were assessed in the isolated rat heart subjected to global ischemia (30 min) followed by reperfusion (60 min) in the presence or absence of superoxide dismutase (5 x 10(4)U/L) plus catalase (7.5 x 10(4)U/L), an antioxidant mixture. The levels of mRNA for the alpha(2), alpha(3), and beta(1) isoforms of Na(+)-K(+) 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(+)-K(+) 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, H(2)O(2) (300 microM), or a free radical generator, xanthine (2mM) plus xanthine oxidase (0.03 U/ml) for 20 min. Perfusion of hearts with H(2)O(2) or xanthine/xanthine oxidase depressed the alpha(2), alpha(3), and beta(1) isoform mRNA levels of the Na(+)-K(+) ATPase, but had lesser effects on alpha(1) mRNA levels. These results indicate that Na(+)-K(+) 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(+)-K(+) ATPase isoform gene expression by ischemia-reperfusion may be mediated by oxidative stress.
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, 351 Tache Avenue Winnipeg, Man., Winnipeg, Canada R2H 2A6.
authors.forename: Petr
authors.initials: P
authors.lastname: Ostadal
authors.forename: Adel B
authors.initials: AB
authors.lastname: Elmoselhi
authors.forename: Irena
authors.initials: I
authors.lastname: Zdobnicka
authors.forename: Anton
authors.initials: A
authors.lastname: Lukas
authors.forename: Donald
authors.initials: D
authors.lastname: Chapman
authors.forename: Naranjan S
authors.initials: NS
authors.lastname: Dhalla
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015152:Blotting, Northern; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis* / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D016877:Oxidants; D020033:Protein Isoforms; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D000254:Sodium-Potassium-Exchanging ATPase