L-Dopa stimulates expression of the antioxidant enzyme NAD(P)H : quinone oxidoreductase (NQO) in cultured astroglial cells

The autooxidation of L-Dopa, a catecholamine used in the symptomatic treatm ent of Parkinson's disease, generally yields reactive oxygen species and ne urotoxic quinones. NAD(P)H:quinone oxidoreductase (NQO) is a flavoenzyme th at is implicated in the detoxication of quinones, including those formed du ring L-Dopa autooxidation. Through the action of this enzyme, deleterious r edox-labile quinones are turned into less toxic and more stable hydroquinon es that are amenable to further detoxication and/or cellular excretion. In the present study, using primary rat astrocytes and C6 astroglioma as a mod el to evaluate the neuroprotective response of astroglial cells upon exposu re to L-Dopa, we demonstrate that this compound, or more correctly its quin one (auto)oxidation products, up-regulates astroglial NQO in a time- and co ncentration-dependent way as assessed at the level of mRNA expression, prot ein level, and enzymatic activity. Moreover, under similar conditions cellu lar glutathione content was enhanced. It is concluded that, similar to glut athione, the oxidative stress Limiting NQO is likely to contribute to the c apacity of astroglial cells to protect dopaminergic neurons against L-Dopa, and, hence, may be considered as a potential target for the development of neuroprotective strategies for Parkinson's disease. (C) 2000 Elsevier Scie nce Inc.