Erythrocyte Copper Chaperone for Superoxide Dismutase Is Increased following Marginal Copper Deficiency in Adult and Postweanling Mice ,

Abstract

A sensitive and reliable biomarker has yet to be identified for marginal copper deficiency in humans. The need for such a biomarker is critical, because increased cases of human copper deficiency evolve following bariatric surgery and other secondary factors besides diet. Four experiments were devised to induce marginal copper deficiency through copper-deficient (CuD) diets (5 wk for mice and 4 wk for rats). In Expt. 1 and 2, male postweanling mice were raised in either solid-bottom plastic cages (Expt. 1) or stainless steel hanging cages (Expt. 2) and compared. Postweanling rats (Expt. 3) and adult mice (Expt. 4) were also studied using stainless steel cages. Copper-adequate controls were fed a semipurified diet containing 9 mg Cu/kg. CuD rats exhibited the most severe changes in biomarkers due to copper limitation, including major reductions in plasma ceruloplasmin (Cp) and erythrocyte superoxide dismutase (Sod1) and augmentation in copper chaperone for Sod1 (CCS). The CuD mice in Expt. 2 were more deficient than the CuD mice in Expt. 1, likely due to coprophagia differences. In fact, the CuD mice in Expt. 1 had unaltered Sod1 or Cp levels. Importantly though, these marginally deficient mice and CuD adult mice that had no changes in Cp activity or liver copper level had robust augmentation of CCS. Erythrocyte CCS was the only consistent biomarker to change in copper deficiency for all dietary groups, suggesting that CCS may be an excellent biomarker for human confirmation of marginal copper deficiency.