Elevated levels of dietary zinc intake modulate the expression of CCS and intestinal zinc trafficking proteins

Experiments were carried out to examine the value of CCS (copper chaperone for CuZn superoxide dismutase) as a novel biomarker of zinc-induced mild copper deficiency and to evaluate the changes in expression of zinc transporters in response to graded levels of moderately high dietary zinc. Weanling male Wistar rats were fed graded levels of zinc (30, 60, 120 and 240 mg zinc/kg diet) for 5 weeks. Results showed a dose-dependent decrease in copper content and an increase in CCS expression in tissues of rats fed the Zn-60 and Zn-120 diets. Surprisingly, rats fed the Zn-240 diet showed better copper status than rats fed the Zn-120 diet. Expression of zinc transporters was significantly upregulated in the small intestine of Zn-240 rats. Collectively, these data show that CCS is responsive to zinc-induced mild copper deficiency, and can serve as a sensitive biomarker of mild copper deficiency. The increased expression of intestinal zinc transporters expression may account for the better copper status of Zn-240 rats