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-AT Pase activity and expression, as well as alterations in membrane lipid composition. The aim of this study was twofold; 1) to document in rat s the effect of streptozotocin-induced diabetes on myocardial Na,K-ATP ase and fatty acids, and 2) to evaluate the potential effect of a diet ary supplementation with fish oil (n-3 fatty acids) on the streptozoto cin-induced changes. Assays were performed in purified cardiac plasma membranes to determine Na,K-ATPase activity, expression of the differe nt 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 anal ysis. Results demonstrated that diabetes significantly decreased activ ities of alpha 1 and alpha 2 isoforms and mRNA levels of alpha 2 and b eta 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 incorporat ion of eicosapentaenoic acid. It also increased the level of beta 1-is oforms and restored the activity of the alpha 2-isoenzyme without sign ificant changes in the level of alpha 1- and alpha 2-isoforms. Norther n blot analysis showed no effect of fish oil supplementation. Experime ntal diabetes and prevention by the fish oil rich (n-3 fatty acids) di et induced specific effects on the activity and expression of ct and b eta Na,K-ATPase subunit isoforms. These studies suggest that fish oil therapy may be effective in preventing some of the adverse consequence s of diabetes.