Abstract
The nuclear transcription factor E2-related factor 2 (Nrf2) has been shown to play pivotal roles in preventing xenobiotic-related toxicity and carcinogen-induced carcinogenesis. These protective roles of Nrf2 have been attributed in part to its involvement in the induction of Phase II drug conjugation/detoxification enzymes as well as antioxidant enzymes through the Nrf2-antioxidant response element (ARE) signaling pathways. This review summarizes the current research status of the identification of Nrf2-regulated drug metabolism enzymes (DMEs), especially Phase II DMEs, and Phase III drug transporters. In addition, the molecular mechanisms underlying the coordinated regulation of Phase II DMEs and Phase III transporters will also be discussed based on findings published in the literature.
2009 John Wiley & Sons, Ltd.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenosine Triphosphate / analogs & derivatives
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Adenosine Triphosphate / metabolism
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Animals
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Anticarcinogenic Agents / pharmacokinetics*
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Carcinogens
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DNA Damage
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Gene Expression Regulation, Enzymologic
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Glucuronosyltransferase / metabolism
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Glutamate-Cysteine Ligase / metabolism
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Humans
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Inactivation, Metabolic / physiology*
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / physiology
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Mice
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Mice, Knockout
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Multidrug Resistance-Associated Proteins
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NF-E2-Related Factor 2 / metabolism*
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NF-kappa B / metabolism
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Pharmaceutical Preparations
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Rats
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Response Elements
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Signal Transduction / drug effects*
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Xenobiotics / pharmacokinetics
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Xenobiotics / pharmacology
Substances
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Anticarcinogenic Agents
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Carcinogens
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Multidrug Resistance-Associated Proteins
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NF-E2-Related Factor 2
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NF-kappa B
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Pharmaceutical Preparations
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Xenobiotics
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2',3'-dialdehyde ATP
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Adenosine Triphosphate
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UDP-glucuronosyltransferase, UGT1A6
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Glucuronosyltransferase
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Glutamate-Cysteine Ligase