Altered expressions of cardiac Na/K-ATPase isoforms in copper deficient rats

OBJECTIVE: The aim was to determine if copper deficiency affects the expression of Na/K-ATPase alpha isoforms in the rat heart. METHODS: Copper deficiency was induced by placing weanling rats on a copper deficient diet for 4-5 weeks. Adult ventricular tissue, isolated ventricular myocytes, and brain stems of the control and deficient rats were compared for Cu, Zn-superoxide dismutase (CuZn-SOD) activity and for protein and mRNA contents of Na/K-ATPase alpha isoforms. RESULTS: In brain stem, where copper deficiency did not alter CuZn-SOD activity, mRNA and protein levels of alpha isoforms also remained unchanged. In ventricular tissue and ventricular myocytes, copper deficiency reduced CuZn-SOD activity, mRNAs of alpha 1 and alpha 2 isoforms, and the alpha 2 isoform protein. The alpha 1 isoform protein of ventricular tissue and its myocytes was marginally reduced by copper deficiency. CONCLUSIONS: In the rat ventricular tissue, oxidative stress resulting from copper deficiency (1) enhances the turnover of the more oxidant sensitive alpha 2 isoform to a greater extent than the turnover of the alpha 1 isoform; (2) regulates mRNA levels of alpha 1 and alpha 2 isoforms; and (3) contributes to the cardiomyopathy of copper deficiency.