Dietary copper deficiency alters protein levels of rat dopamine beta-monooxygenase and tyrosine monooxygenase

Perinatal copper (Cu) deficiency was studied by offering pregnant Sprague Dawley rats a basal diet low in copper, 0.44 mg/kg, and drinking water containing 0 (-Cu) or 20 (+Cu) mg Cu/L as CuSO4 starting at day 7 of gestation and continuing throughout lactation. To investigate dopamine-beta-monooxygenase (DBM) and tyrosine monooxygenase (TM) in adrenal gland and brain, offspring were weaned at Day 21 to treatments of their respective dams for 9 days. Offspring, 30 days old, of Cu-deficient (-Cu) dams were smaller, anemic, and had biochemical features characteristic of severe Cu deficiency. Adrenal DBM enzyme activity of 30-day-old -Cu rats was 40% higher than Cu-adequate (+Cu) rats and DBM protein levels, estimated by Western immunoblot, were 45% higher. Adrenal DBM mRNA levels of -Cu rats were 108% higher than +Cu rats. Adrenal TM protein levels of -Cu rats were 39% higher than +Cu rats. Hypothalamus DBM activity was significantly higher in -Cu than +Cu rats but no reproducible changes in DBM or TM protein levels could be detected by Western immunoblots. Diet history did not impact adrenal gland or hypothalamus levels of actin as detected on reblotted membranes. However, activity of the cuproenzyme Cu,Zn-superoxide dismutase was 50% lower and 30% lower, respectively, in extracts from rat adrenal gland and hypothalamus of -Cu than +Cu rats, indicating altered Cu status in the tissues studied. These data suggest that Cu deficiency is associated with increased formation of DBM and TM protein levels in adrenal gland. Further research will be required to determine the chemical signal responsible for this induction and if DBM or TM protein levels change in other tissues.