NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a multifunctional antioxidant enzyme and exceptionally versatile cytoprotector

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    Abstract

    NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1) is a widely-distributed FAD-dependent flavoprotein that promotes obligatory 2-electron reductions of quinones, quinoneimines, nitroaromatics, and azo dyes, at rates that are comparable with NADH or NADPH. These reductions depress quinone levels and thereby minimize opportunities for generation of reactive oxygen intermediates by redox cycling, and for depletion of intracellular thiol pools. NQO1 is a highly-inducible enzyme that is regulated by the Keap1/Nrf2/ARE pathway. Evidence for the importance of the antioxidant functions of NQO1 in combating oxidative stress is provided by demonstrations that induction of NQO1 levels or their depletion (knockout, or knockdown) are associated with decreased and increased susceptibilities to oxidative stress, respectively. Furthermore, benzene genotoxicity is markedly enhanced when NQO1 activity is compromised. Not surprisingly, human polymorphisms that suppress NQO1 activities are associated with increased predisposition to disease. Recent studies have uncovered protective roles for NQO1 that apparently are unrelated to its enzymatic activities. NQO1 binds to and thereby stabilizes the important tumor suppressor p53 against proteasomal degradation. Indeed. NQO1 appears to regulate the degradative fate of other proteins. These findings suggest that NQO1 may exercise a selective "gatekeeping" role in regulating the proteasomal degradation of specific proteins, thereby broadening the cytoprotective role of NQO1 far beyond its highly effective antioxidant functions. (C) 2010 Elsevier Inc. All rights reserved.

    Original languageEnglish
    Pages (from-to)116-123
    Number of pages8
    JournalArchives of Biochemistry and Biophysics
    Volume501
    Issue number1
    DOIs
    Publication statusPublished - 1 Sep 2010

    Keywords

    • Antioxidant response element (ARE)
    • Benzene toxicity
    • Estrogen quinone
    • Keap1
    • Microtubule stability
    • Nrf2
    • Oxidative stress
    • p53
    • Proteasomal degradation
    • 20S PROTEASOMAL DEGRADATION
    • CUL3-BASED E3 LIGASE
    • DNA ADDUCT FORMATION
    • NAD(P)H-QUINONE OXIDOREDUCTASE-1
    • QUINONE OXIDOREDUCTASE-1
    • OXIDATIVE STRESS
    • DT-DIAPHORASE
    • ALZHEIMERS-DISEASE
    • RESPONSE ELEMENT
    • NEUROBLASTOMA-CELLS

    Cite this

    @article{530626ee2a694e53af4e6382844747bb,
    title = "NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a multifunctional antioxidant enzyme and exceptionally versatile cytoprotector",
    abstract = "NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1) is a widely-distributed FAD-dependent flavoprotein that promotes obligatory 2-electron reductions of quinones, quinoneimines, nitroaromatics, and azo dyes, at rates that are comparable with NADH or NADPH. These reductions depress quinone levels and thereby minimize opportunities for generation of reactive oxygen intermediates by redox cycling, and for depletion of intracellular thiol pools. NQO1 is a highly-inducible enzyme that is regulated by the Keap1/Nrf2/ARE pathway. Evidence for the importance of the antioxidant functions of NQO1 in combating oxidative stress is provided by demonstrations that induction of NQO1 levels or their depletion (knockout, or knockdown) are associated with decreased and increased susceptibilities to oxidative stress, respectively. Furthermore, benzene genotoxicity is markedly enhanced when NQO1 activity is compromised. Not surprisingly, human polymorphisms that suppress NQO1 activities are associated with increased predisposition to disease. Recent studies have uncovered protective roles for NQO1 that apparently are unrelated to its enzymatic activities. NQO1 binds to and thereby stabilizes the important tumor suppressor p53 against proteasomal degradation. Indeed. NQO1 appears to regulate the degradative fate of other proteins. These findings suggest that NQO1 may exercise a selective {"}gatekeeping{"} role in regulating the proteasomal degradation of specific proteins, thereby broadening the cytoprotective role of NQO1 far beyond its highly effective antioxidant functions. (C) 2010 Elsevier Inc. All rights reserved.",
    keywords = "Antioxidant response element (ARE), Benzene toxicity, Estrogen quinone, Keap1, Microtubule stability, Nrf2, Oxidative stress, p53, Proteasomal degradation, 20S PROTEASOMAL DEGRADATION, CUL3-BASED E3 LIGASE, DNA ADDUCT FORMATION, NAD(P)H-QUINONE OXIDOREDUCTASE-1, QUINONE OXIDOREDUCTASE-1, OXIDATIVE STRESS, DT-DIAPHORASE, ALZHEIMERS-DISEASE, RESPONSE ELEMENT, NEUROBLASTOMA-CELLS",
    author = "Dinkova-Kostova, {Albena T.} and Paul Talalay",
    year = "2010",
    month = "9",
    day = "1",
    doi = "10.1016/j.abb.2010.03.019",
    language = "English",
    volume = "501",
    pages = "116--123",
    journal = "Archives of Biochemistry and Biophysics",
    issn = "0003-9861",
    publisher = "Elsevier",
    number = "1",

    }

    TY - JOUR

    T1 - NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a multifunctional antioxidant enzyme and exceptionally versatile cytoprotector

    AU - Dinkova-Kostova, Albena T.

    AU - Talalay, Paul

    PY - 2010/9/1

    Y1 - 2010/9/1

    N2 - NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1) is a widely-distributed FAD-dependent flavoprotein that promotes obligatory 2-electron reductions of quinones, quinoneimines, nitroaromatics, and azo dyes, at rates that are comparable with NADH or NADPH. These reductions depress quinone levels and thereby minimize opportunities for generation of reactive oxygen intermediates by redox cycling, and for depletion of intracellular thiol pools. NQO1 is a highly-inducible enzyme that is regulated by the Keap1/Nrf2/ARE pathway. Evidence for the importance of the antioxidant functions of NQO1 in combating oxidative stress is provided by demonstrations that induction of NQO1 levels or their depletion (knockout, or knockdown) are associated with decreased and increased susceptibilities to oxidative stress, respectively. Furthermore, benzene genotoxicity is markedly enhanced when NQO1 activity is compromised. Not surprisingly, human polymorphisms that suppress NQO1 activities are associated with increased predisposition to disease. Recent studies have uncovered protective roles for NQO1 that apparently are unrelated to its enzymatic activities. NQO1 binds to and thereby stabilizes the important tumor suppressor p53 against proteasomal degradation. Indeed. NQO1 appears to regulate the degradative fate of other proteins. These findings suggest that NQO1 may exercise a selective "gatekeeping" role in regulating the proteasomal degradation of specific proteins, thereby broadening the cytoprotective role of NQO1 far beyond its highly effective antioxidant functions. (C) 2010 Elsevier Inc. All rights reserved.

    AB - NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1) is a widely-distributed FAD-dependent flavoprotein that promotes obligatory 2-electron reductions of quinones, quinoneimines, nitroaromatics, and azo dyes, at rates that are comparable with NADH or NADPH. These reductions depress quinone levels and thereby minimize opportunities for generation of reactive oxygen intermediates by redox cycling, and for depletion of intracellular thiol pools. NQO1 is a highly-inducible enzyme that is regulated by the Keap1/Nrf2/ARE pathway. Evidence for the importance of the antioxidant functions of NQO1 in combating oxidative stress is provided by demonstrations that induction of NQO1 levels or their depletion (knockout, or knockdown) are associated with decreased and increased susceptibilities to oxidative stress, respectively. Furthermore, benzene genotoxicity is markedly enhanced when NQO1 activity is compromised. Not surprisingly, human polymorphisms that suppress NQO1 activities are associated with increased predisposition to disease. Recent studies have uncovered protective roles for NQO1 that apparently are unrelated to its enzymatic activities. NQO1 binds to and thereby stabilizes the important tumor suppressor p53 against proteasomal degradation. Indeed. NQO1 appears to regulate the degradative fate of other proteins. These findings suggest that NQO1 may exercise a selective "gatekeeping" role in regulating the proteasomal degradation of specific proteins, thereby broadening the cytoprotective role of NQO1 far beyond its highly effective antioxidant functions. (C) 2010 Elsevier Inc. All rights reserved.

    KW - Antioxidant response element (ARE)

    KW - Benzene toxicity

    KW - Estrogen quinone

    KW - Keap1

    KW - Microtubule stability

    KW - Nrf2

    KW - Oxidative stress

    KW - p53

    KW - Proteasomal degradation

    KW - 20S PROTEASOMAL DEGRADATION

    KW - CUL3-BASED E3 LIGASE

    KW - DNA ADDUCT FORMATION

    KW - NAD(P)H-QUINONE OXIDOREDUCTASE-1

    KW - QUINONE OXIDOREDUCTASE-1

    KW - OXIDATIVE STRESS

    KW - DT-DIAPHORASE

    KW - ALZHEIMERS-DISEASE

    KW - RESPONSE ELEMENT

    KW - NEUROBLASTOMA-CELLS

    U2 - 10.1016/j.abb.2010.03.019

    DO - 10.1016/j.abb.2010.03.019

    M3 - Review article

    C2 - 20361926

    VL - 501

    SP - 116

    EP - 123

    JO - Archives of Biochemistry and Biophysics

    JF - Archives of Biochemistry and Biophysics

    SN - 0003-9861

    IS - 1

    ER -