Reciprocal regulation of the content of aromatic L-amino acid decarboxylase and tyrosine hydroxylase mRNA by NGF in PC12 cells

Abstract

Aromatic L-amino acid decarboxylase (AADC) and tyrosine hydroxylase (TH) are involved in the synthesis of dopamine and other monoamine neurotransmitters, and their activities can be regulated by a number of physiological stimuli. An interesting finding has been that (-)-deprenyl and some other irreversible monoamine B oxidase inhibitors increase AADC gene expression and that these compounds can exert neuronal protection/rescue effects. In this study, we have investigated the effects of nerve growth factor (NGF), and of (-)-deprenyl on AADC and TH gene expression in PC12 cells. Cells were treated with different doses of NGF (0.2-50 ng/ml) for up to 3 days. Northern and blot hybridizations were performed to detect AADC and TH mRNA. The results show that NGF can down-regulate AADC gene expression while increasing TH gene expression in a time- and dose-dependent fashion. Treatment with (-)-deprenyl alone increases the gene expression of AADC, and (-)-deprenyl further counteracts the reductions induced by NGF. This study introduces novel results with regard to the regulation of the gene expression of AADC in PC12 cells, which is not paralleled by the other catecholamine biosynthetic enzymes. These findings support the existence of an interaction between NGF and AADC gene expression that may be associated with the process of neuronal degeneration or regeneration.