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 treatment of Parkinson's disease, generally yields reactive oxygen species and neurotoxic quinones. NAD(P)H:quinone oxidoreductase (NQO) is a flavoenzyme that is implicated in the detoxication of quinones, including those formed during L-Dopa autooxidation. Through the action of this enzyme, deleterious redox-labile quinones are turned into less toxic and more stable hydroquinones that are amenable to further detoxication and/or cellular excretion. In the present study, using primary rat astrocytes and C6 astroglioma as a model to evaluate the neuroprotective response of astroglial cells upon exposure to L-Dopa, we demonstrate that this compound, or more correctly its quinone (auto)oxidation products, up-regulates astroglial NQO in a time- and concentration-dependent way as assessed at the level of mRNA expression, protein level, and enzymatic activity. Moreover, under similar conditions cellular glutathione content was enhanced. It is concluded that, similar to glutathione, the oxidative stress limiting NQO is likely to contribute to the capacity 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.
van Muiswinkel
F L
FL
Research Institute Neurosciences Vrije Universiteit, Departments of Psychiatry and Neurology, Amsterdam, The Netherlands.
Riemers
F M
FM
Peters
G J
GJ
LaFleur
M V
MV
Siegel
D
D
Jongenelen
C A
CA
Drukarch
B
B
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000201:enzymology*; D001254:Astrocytoma; D002478:Cells, Cultured; D001728:Dicumarol / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D016133:Polymerase Chain Reaction; D051381:Rats; D014407:Tumor Cells, Cultured
D007980:Levodopa; D001728:Dicumarol; D016660:NAD(P)H Dehydrogenase (Quinone); D007213:Indomethacin