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- W2024036433 abstract "UDP-glucuronosyltransferases (UGTs) catalyze a major Phase II reaction in the endo- and xenobiotic-metabolizing enzyme (XME) system consisting of Phases I-III proteins and ligand-activated transcription factors. Differential induction of liver microsomal CYP activities following treatment of rats with aryl hydrocarbons or phenobarbital, discovered over 50 years ago, initiated studies to characterize multiple CYPs and the transcription factors Ah receptor (AhR) and CAR, respectively. Similar studies of UGT activities initiated studies of multiple UGTs. However, inducible human UGTs differed from those in rats. In addition, induction of UGTs is complicated, for example, by coordinate regulation of some XMEs by AhR and the antioxidant Nrf2 transcription factor. Functions of UGTs in the XME system are discussed using the following examples: (i) Tight coupling between Phase I and II enzymes in benzo[a]pyrene detoxification. In particular, AhR- and Nrf2-controlled quinone reductases and UGTs may prevent quinone-quinol redox cycling with generation of oxidative stress. (ii) CAR-mediated induction of UGT1A1 may be involved in perinatal detoxification of bilirubin neurotoxicity. (iii) PPARα-mediated glucuronidation of eicosanoids may contribute to their detoxification and homeostasis. Identification of the role of UGTs is challenged by intense crosstalk of transcription factors at the genetic level, the level of protein-protein interaction and control by signaling networks. Nevertheless, as drug targets ligand-activated transcription factors provide promising therapeutic possibilities." @default.
- W2024036433 created "2016-06-24" @default.
- W2024036433 creator A5032074919 @default.
- W2024036433 date "2011-07-01" @default.
- W2024036433 modified "2023-09-26" @default.
- W2024036433 title "From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans" @default.
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