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• W1984534635 endingPage "e39006" @default.
• W1984534635 startingPage "e39006" @default.
• W1984534635 abstract "Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that induces a battery of cytoprotective genes in response to oxidative/electrophilic stress. Kelch-like ECH associating protein 1 (Keap1) sequesters Nrf2 in the cytosol. The purpose of this study was to investigate the role of Nrf2 in regulating the mRNA of genes encoding drug metabolizing enzymes and xenobiotic transporters. Microarray analysis was performed in livers of Nrf2-null, wild-type, Keap1-knockdown mice with increased Nrf2 activation, and Keap1-hepatocyte knockout mice with maximum Nrf2 activation. In general, Nrf2 did not have a marked effect on uptake transporters, but the mRNAs of organic anion transporting polypeptide 1a1, sodium taurocholate cotransporting polypeptide, and organic anion transporter 2 were decreased with Nrf2 activation. The effect of Nrf2 on cytochrome P450 (Cyp) genes was minimal, with only Cyp2a5, Cyp2c50, Cyp2c54, and Cyp2g1 increased, and Cyp2u1 decreased with enhanced Nrf2 activation. However, Nrf2 increased mRNA of many other phase-I enzymes, such as aldo-keto reductases, carbonyl reductases, and aldehyde dehydrogenase 1. Many genes involved in phase-II drug metabolism were induced by Nrf2, including glutathione S-transferases, UDP- glucuronosyltransferases, and UDP-glucuronic acid synthesis enzymes. Efflux transporters, such as multidrug resistance-associated proteins, breast cancer resistant protein, as well as ATP-binding cassette g5 and g8 were induced by Nrf2. In conclusion, Nrf2 markedly alters hepatic mRNA of a large number of drug metabolizing enzymes and xenobiotic transporters, and thus Nrf2 plays a central role in xenobiotic metabolism and detoxification." @default.
• W1984534635 created "2016-06-24" @default.
• W1984534635 creator A5076743166 @default.
• W1984534635 creator A5083842467 @default.
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• W1984534635 date "2012-07-12" @default.
• W1984534635 modified "2023-09-30" @default.
• W1984534635 title "Effect of Graded Nrf2 Activation on Phase-I and -II Drug Metabolizing Enzymes and Transporters in Mouse Liver" @default.
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• W1984534635 doi "https://doi.org/10.1371/journal.pone.0039006" @default.
• W1984534635 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3395627" @default.
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• W1984534635 hasPublicationYear "2012" @default.
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