Biomarker erythrocyte copper chaperone for superoxide dismutase (CCS) is higher following marginal copper deficiency

Abstract

There is a critical need to identify an accurate copper biomarker to diagnose and treat adult onset copper deficiency. Prevalence is rising due to secondary impacts of antagonists such as zinc and popularity of bariatric surgery. Marginal copper deficiency (CuM) and iron deficiency (FeD) were studied in Sprague Dawley rat and Swiss Webster mouse models using modified AIN‐93G diets. Red blood cell (RBC) superoxide dismutase (Sod1) and plasma ceruloplasmin (Cp) protein were found to be altered by both FeD and copper deficiency (CuD), while CCS and CCS/Sod1 ratio were found only to be altered in CuD rats; and importantly, after only 1 week of treatment in post weanling males. RBC CCS levels were highly negatively correlated, r = −0.91, with liver copper in CuD, CuM and copper adequate (CuA) rats. Post weanling CuD male mice reared in plastic cages for 5 weeks had no significant reduction in liver copper, plasma Cp protein, or RBC Sod1 compared to CuA mice but CuD mice displayed 2‐fold higher RBC CCS. CuD adult male mice with no significant changes in Cp activity and protein after 5 weeks of dietary treatment displayed augmented RBC CCS. Additional research is needed to establish that erythrocyte CCS is a suitable copper biomarker for humans but RBC CCS appears to be a robust marker for marginal copper deficiency in rodent models.Supported by the International Copper Association and USDA NIFA 2006‐35200‐17378.