Expression of NAD(P)H:quinone oxidoreductase in the normal and Parkinsonian substantia nigra.
Dopamine (DA) autooxidation, and consequent formation of neurotoxic DA-derived quinones and reactive oxygen species, has been implicated in dopaminergic cell death and, hence, in the pathogenesis of Parkinson's disease (PD). Stimulation of pathways involved in the detoxication of DA-quinones in the brain is hypothesized to be an effective means to limit oxidative stress and to confer neuroprotection in PD. In this respect, the inducible flavoprotein NAD(P)H:quinone oxidoreductase (NQO1) is of particular interest as it is directly implicated in the detoxication of DA-quinones and, in addition, has broad spectrum anti-oxidant properties. To study the potential pathophysiological role of NQO1 in PD, the cellular expression of NQO1 was examined in the mesencephalon of PD patients and age-matched controls. In the substantia nigra pars compacta (SNpc), NQO1 was found to be expressed in astroglial and endothelial cells and, albeit less frequently, also in dopaminergic neurons. Moreover, while overt NQO1 immunoreactivity was absent in the surrounding nervous tissue, in the Parkinsonian SNpc a marked increase in the astroglial and neuronal expression of NQO1 was consistently observed.
van Muiswinkel
F L
FL
Department of Medical Pharmacology, Institute for Clinical and Experimental Neurosciences (ICEN), VU University Medical Center, Vrije Universiteit, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. F.L.vanMuiswinkel@neuro.azu.nl
de Vos
R A I
RA
Bol
J G J M
JG
Andringa
G
G
Jansen Steur
E N H
EN
Ross
D
D
Siegel
D
D
Drukarch
B
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000201:enzymology / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D010300:Parkinson Disease / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013378:Substantia Nigra / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology
D017382:Reactive Oxygen Species; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D004298:Dopamine