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

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Abstract
Objective: The aim was to determine if copper deficiency affects the expression of Na/K-ATPase α 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 a isoforms. Results: In brain stem, where copper deficiency did not alter CuZn-SOD activity, mRNA and protein levels of α isoforms also remained unchanged. In ventricular tissue and ventricular myocytes, copper deficiency reduced CuZn-SOD activity, mRNAs of α1 and α2 isoforms, and the α2 isoform protein. The α1 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 α2 isoform to a greater extent than the turnover of the α1 isoform; (2) regulates mRNA levels of α1 and α2 isoforms; and (3) contributes to the cardiomyopathy of copper deficiency.

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