Differential impact of copper deficiency in rats on blood cuproproteins.

Sensitive blood biochemical markers of dietary copper status are not yet known. Rat models were used to investigate the response of severe copper deficiency in dams and pups by comparing abundance of several cuproproteins in erythrocytes, white blood cells, and platelets. The hypothesis tested was that copper deficiency would result in changes in abundance of cuproproteins in blood cells. Copper-deficient (CuD) Holtzman dams and pups had signs consistent with severe copper deficiency compared with copper-adequate controls including lower liver copper and hemoglobin levels and near total loss of plasma ceruloplasmin diamine oxidase activity. Copper-deficient erythrocytes had lower copper, zinc superoxide dismutase (SOD1) but higher copper metallochaperone for SOD1 (CCS) compared with copper-adequate, resulting in higher CCS/SOD1 levels. This ratio was more sensitive in CuD erythrocytes than CuD white cells and especially in CuD platelets. However, both white blood cells and platelets from CuD dams and pups had nearly nondetectable levels of cytochrome c oxidase subunit IV. Because isolation of relatively pure populations of erythrocytes and platelets is feasible, and reagents for immunoblot methods are available, determination of CCS/SOD1 and cytochrome c oxidase subunit IV protein levels may be useful to assess copper status of humans.