Alterations of Rat Brain Peptidylglycine α-Amidating Monooxygenase and Other Cuproenzyme Activities Following Perinatal Copper Deficiency

Abstract

Perinatal copper (Cu) deficiency was studied in month-old female and male Sprague-Dawley rat offspring to investigate regional changes in brain cuproenzymes. Offspring of dams given the low Cu treatment beginning at Day 7 of gestation exhibited signs characteristic of Cu deficiency including a 70% reduction in liver Cu levels compared with Cu-adequate controls. Compared with Cu-adequate rats, Cu-deficient rats had lower activities of the cuproenzymes peptidylglycine α-amidating monooxygenase (PAM), cytochrome c oxydase (CCO), and Cu, Zn-superoxide dismutase (SOD) in all six brain regions studied. Apparent activity of dopamine-β-monooxygenase (DBM) was higher in all regions from Cu-deficient compared with Cu-adequate rats. Activity of the selenoenzyme glutathione peroxidase (GPX) was not greatly altered in brain by Cu deficiency. Following 1 month of Cu repletion, liver but not brain Cu levels were equivalent to control. Brain CCO activity was still lower in Cu-repleted female and male rats. PAM activity was still lower in cerebrum of Cu-repleted rats. DBM activity was no longer significantly elevated in the former Cu-deficient groups except for midbrain. SOD and GPX activity were equivalent between groups. PAM activity, in vitro, is lower in the brain following perinatal Cu deficiency and activity is slow to recover following nutritional supplementation with Cu. Perhaps neuropeptide maturation is compromised by Cu deficiency.