Ischemia-reperfusion alters gene expression of Na+-K+ 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(+)-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.
Ostadal
Petr
P
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.
Elmoselhi
Adel B
AB
Zdobnicka
Irena
I
Lukas
Anton
A
Chapman
Donald
D
Dhalla
Naranjan S
NS
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
D000975:Antioxidants; D016877:Oxidants; D020033:Protein Isoforms; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D000254:Sodium-Potassium-Exchanging ATPase