NAD(P)H:quinone oxidoreductase 1 expression in multiple sclerosis lesions

Jack van Horssen, Gerty Schreibelt, Lars Bö, Lisette Montagne, Benjamin Drukarch, Freek L van Muiswinkel, Helga E de Vries

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)311-7
Number of pages7
JournalFree Radical Biology and Medicine
Volume41
Issue number2
DOIs
Publication statusPublished - 15 Jul 2006

Cite this

van Horssen, Jack ; Schreibelt, Gerty ; Bö, Lars ; Montagne, Lisette ; Drukarch, Benjamin ; van Muiswinkel, Freek L ; de Vries, Helga E. / NAD(P)H:quinone oxidoreductase 1 expression in multiple sclerosis lesions. In: Free Radical Biology and Medicine. 2006 ; Vol. 41, No. 2. pp. 311-7.
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abstract = "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.",
keywords = "Adult, Aged, Aged, 80 and over, Female, Humans, Immunohistochemistry, Male, Middle Aged, Multiple Sclerosis, NAD(P)H Dehydrogenase (Quinone), Journal Article, Research Support, Non-U.S. Gov't",
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NAD(P)H:quinone oxidoreductase 1 expression in multiple sclerosis lesions. / van Horssen, Jack; Schreibelt, Gerty; Bö, Lars; Montagne, Lisette; Drukarch, Benjamin; van Muiswinkel, Freek L; de Vries, Helga E.

In: Free Radical Biology and Medicine, Vol. 41, No. 2, 15.07.2006, p. 311-7.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - NAD(P)H:quinone oxidoreductase 1 expression in multiple sclerosis lesions

AU - van Horssen, Jack

AU - Schreibelt, Gerty

AU - Bö, Lars

AU - Montagne, Lisette

AU - Drukarch, Benjamin

AU - van Muiswinkel, Freek L

AU - de Vries, Helga E

PY - 2006/7/15

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N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Female

KW - Humans

KW - Immunohistochemistry

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis

KW - NAD(P)H Dehydrogenase (Quinone)

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.freeradbiomed.2006.04.013

DO - 10.1016/j.freeradbiomed.2006.04.013

M3 - Article

VL - 41

SP - 311

EP - 317

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 2

ER -