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

Perinatal copper (Cu) deficiency was studied by offering pregnant Sprague D awley rats a basal diet low in copper, 0.44 mg/ kg, end drinking water cont aining 0 (-Cu) or 20 (+Cu) mg Cult as CuSO4 starting at day 7 of gestation and continuing throughout lactation. To investigate dopamine-p-monooxygenas e (DBM) and tyrosine monooxygenase (TM) in adrenal gland and brain, offspri ng were weaned at Day 21 to treatments of their respective darns for 9 days . Offspring, 30 days old, of Cu-deficient (-Cu) dams were smaller, anemic, and had biochemical features characteristic of severe Cu deficiency. Adrena l DBM enzyme activity of 10-day-old -Cu rats was 40% higher than Cu-adequat e (+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 r ats. Adrenal TM protein levels of -Cu rats were 39% higher than +Cu rats. H ypothalamus DBM activity was significantly higher in -Cu than +Cu rats but no reproducible changes in DBM or TM protein levels could be detected by We stern immunoblots. Diet history did not impact adrenal gland or hypothalamu s levels of actin as detected on reblotted membranes. However, activity of the cuproenzyme Cu,Zn-superoxide dismutase was 50% lower and 30% lower, res pectively, in extracts from rat adrenal gland and hypothalamus of -Cu than +Cu rats, indicating altered Cu status in the tissues studied. These data s uggest that Cu deficiency is associated with increased formation of DBM and TM protein levels in adrenal gland. Further research will be required to d etermine the chemical signal responsible for this induction and if DBM or T M protein levels change in other tissues.