Copper deficiency in rodents alters dopamine beta-mono-oxygenase activity, mRNA and protein level

Cu is an essential cofactor for at least twelve mammalian enzymes including dopamine beta-mono-oxygenase (DBM), which converts dopamine (DA) to noradrenaline (NA). Previous studies reported that certain Cu-deficient (Cu-) rat tissues have lower NA and higher DA than Cu-adequate (Cu+) tissues, suggesting that DBM function was impaired. However, in vitro studies suggested that DBM activity is higher in Cu- tissue. Experiments were conducted on adrenal glands (AG), medulla oblongata/pons (MO), vas deferens (VD) and heart (HT) from a single rat experiment to provide data to help clarify this puzzling contradiction. In vitro DBM activity assays showed Cu- samples had significantly higher activity than Cu+ samples in both AG and MO, but not VD. Activity data were confirmed by Western immunoblots. Quantitative real-time PCR demonstrated higher DBM mRNA in Cu- tissues but unaltered levels of several other cuproenzymes and Cu-binding proteins. Previous pharmacological data implied that high DBM was associated with low NA. HPLC analyses confirmed that NA and DA levels in Cu- MO, VD and HT were significantly lower and higher, respectively, than in Cu+ tissues. However, the NA content of AG was not statistically lower. Furthermore there was no correlation between higher DBM mRNA and lower NA in four Cu-tissues. Adequate dietary Cu is essential to support DBM function in vivo but additional studies are needed to determine the mechanism for increased DBM transcription associated with Cu deficiency.