NAD(P)H:quinone oxidoreductase 1 expression in multiple sclerosis lesions.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), marked by infiltration of monocyte-derived macrophages in the brain parenchyma. Macrophages contribute to disease pathology by secretion of inflammatory mediators, such as reactive oxygen species (ROS). ROS are involved in various processes underlying MS pathology, including monocyte migration across the blood-brain barrier, phagocytosis and degradation of myelin, axonal degeneration, and oligodendrocyte damage. High concentrations of ROS cause oxidative stress, which induces transcriptional activation of phase II detoxification enzymes, such as the antioxidant protein NAD(P)H:quinone oxidoreductase 1 (NQO1). Since NQO1 expression may act as an indicator of oxidative stress and knowledge about the cellular distribution pattern of NQO1 in MS brains is lacking, we examined the expression of NQO1 in various well-characterized MS lesions. Here, we show for the first time that NQO1 is highly upregulated in active and chronic active MS lesions, particularly in hypertrophic astrocytes and myelin-laden macrophages. We hypothesize that increased NQO1 expression may reflect an endogenous defense response against ROS-mediated cellular toxicity. Compounds that induce the production of endogenous antioxidant enzymes, such as NQO1, may be potential targets for future treatment strategies in MS.
van Horssen
Jack
J
Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. j.vanhorssen@vumc.nl
Schreibelt
Gerty
G
Bö
Lars
L
Montagne
Lisette
L
Drukarch
Benjamin
B
van Muiswinkel
Freek L
FL
de Vries
Helga E
HE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000201:enzymology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*
D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human