Alteration of Na,K-ATPase isoenzymes in diabetic cardiomyopathy: effect of dietary supplementation with fish oil (n-3 fatty acids) in rats.
Diabetic cardiomyopathy has been associated with a decrease in Na,K-ATPase activity and expression, as well as alterations in membrane lipid composition. The aim of this study was twofold: 1) to document in rats the effect of streptozotocin-induced diabetes on myocardial Na,K-ATPase and fatty acids, and 2) to evaluate the potential effect of a dietary supplementation with fish oil (n-3 fatty acids) on the streptozotocin-induced changes. Assays were performed in purified cardiac plasma membranes to determine Na,K-ATPase activity, expression of the different alpha- and beta-subunits of Na,K-ATPase, and the fatty acid content of total phospholipids. Relative abundance of the mRNAs encoding the alpha 1, alpha 2 and beta 1 isoforms was studied by Northern blot analysis. Results demonstrated that diabetes significantly decreased activities of alpha 1 and alpha 2 isoforms and mRNA levels of alpha 2 and beta 1 isoforms, and, at the protein level, increased alpha 1-isoforms and decreased both alpha 2- and beta 1-isoforms. Changes in fatty acid content of the membrane were consistent with inhibition of desaturase. Fish-oil supplementation produced an increase in membrane incorporation of eicosapentaenoic acid. It also increased the level of beta 1-isoforms and restored the activity of the alpha 2-isoenzyme without significant changes in the level of alpha 1- and alpha 2-isoforms. Northern blot analysis showed no effect of fish oil supplementation. Experimental diabetes and prevention by the fish oil rich (n-3 fatty acids) diet induced specific effects on the activity and expression of alpha and beta Na,K-ATPase subunit isoforms. These studies suggest that fish oil therapy may be effective in preventing some of the adverse consequences of diabetes.
Gerbi
A
A
Laboratoire de Diabetologie, Marseille, France.
Barbey
O
O
Raccah
D
D
Coste
T
T
Jamme
I
I
Nouvelot
A
A
Ouafik
L
L
Lévy
S
S
Vague
P
P
Maixent
J M
JM
D000704:Analysis of Variance; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D009202:Cardiomyopathies / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D008076:Cholesterol, HDL / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology / Q000503:physiopathology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005395:Fish Oils / Q000494:pharmacology*; D005527:Food, Fortified; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D000069463:Olive Oil; D010743:Phospholipids / Q000378:metabolism; D010938:Plant Oils / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000378:metabolism*
D008076:Cholesterol, HDL; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D007527:Isoenzymes; D000069463:Olive Oil; D010743:Phospholipids; D010938:Plant Oils; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase