کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2513278 1118404 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans
چکیده انگلیسی

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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 82, Issue 1, 1 July 2011, Pages 9–16
نویسندگان
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