Copper deficiency induces the upregulation of the copper chaperone for Cu/Zn superoxide dismutase in weanling male rats

The most commonly used indices for determining copper deficiency in humans are reduced serum/plasma copper concentration and decreased activity of ceruloplasmin and Cu/Zn superoxide dismutase (SOD1). However, these indicators are influenced by many factors unrelated to copper status and lack the sensitivity required to detect marginal deficiency, limiting their usefulness in many situations. In vivo, the insertion of copper into SOD1 is dependent on the copper chaperone for SOD1 (CCS). In this study, we explored the possibility that the expression level of CCS may reflect copper status and thus serve as a useful marker of copper nutriture. Weanling male Wistar rats were fed either a normal (5.3 mg Cu/kg diet), moderately deficient (0.84 mg Cu/kg diet) or deficient (0.34 mg Cu/kg diet) copper diet for 6 wk. Rats fed moderate and deficient diets showed differences (P < 0.05) in several hematological measurements, indicating varying degrees of copper deficiency in these groups. Copper-deficient rats had reduced (P < 0.05) liver and erythrocyte SOD1 activity and body weight. Western blot analysis revealed a dose-dependent increase (P < 0.05) in CCS expression in liver and erythrocytes of copper-deficient rats. We report CCS protein level as a novel marker for assessing copper status.