Variable response of selected cuproproteins in rat choroid plexus and cerebellum following perinatal copper deficiency

Recent immunohistochemical characterization of the copper transport protein, Ctr1, reported enriched levels in mouse choroid plexus, and enhancement by copper deficiency. To extend and confirm this, experiments were conducted with Holtzman rats. Following perinatal copper deficiency there was an 80% reduction in brain copper of 24-27 day old copper-deficient (Cu-) rat pups compared to copper-adequate (Cu+) controls. Choroid plexus immunoblot analysis with rabbit anti-hCtr1 demonstrated a 50% higher Ctr1 protein expression in Cu- samples. However, levels of copper chaperone for superoxide dismutase (CCS) were unchanged, suggesting that Ctr1 buffers the choroid plexus against copper deficiency, since CCS normally is much higher in Cu- tissues. There were 13% lower levels of cytochrome c oxidase subunit IV ( COX IV) detected in Cu- choroid plexus. In contrast, in cerebellum of Cu- rats CCS was 2-fold higher and COX IV 1.7-fold lower than Cu+ rats consistent with severe copper deficiency. Brain mitochondria from Cu- rats had severe reductions in COX IV content and CCO activity and modest but significant elevations in CCS and reductions in Cu, Zn- superoxide dismutase. COX IV may be a more sensitive marker for copper deficiency than CCS and may prove useful to assess copper status.