| Human UDP-glucuronosyltransferases: Feedback loops between substrates and ligands of their transcription factors. | |
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MedLine Citation:
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PMID: 22820246 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Expression profiles of human adult and fetal hepatic and intestinal UDP-glucuronosyltransferases (UGTs), information about their endo- and xenobiotic substrates, and their transcriptional regulation suggest regulatory circuits between some UGT substrates and ligands of their transcription factors. For examples: (i) Bilirubin is solely conjugated by UGT1A1 and activates its transcription factors Ah receptor, PXR and CAR. (ii) Hepatotoxic lithocholic acid (LCA) is oxidized to hyodeoxycholic acid, the latter conjugated by UGT2B4 and UGT2B7. LCA is also an agonist of FXR and PPARα which are controlling these UGTs. (iii) Similar feedback loops possibly exist between some eicosanoids, PPARα and UGTs. (iiii) Regulatory circuits may also have evolved between dietary polyphenols which are efficient substrates of UGTs and activators of the Ah receptor. Although many newly developed drugs are conjugated by promiscuous UGTs, the discussed regulatory circuits may provide hints to evolutionary important UGT substrates. |
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Authors:
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Karl Walter Bock |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-7-17 |
Journal Detail:
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Title: Biochemical pharmacology Volume: - ISSN: 1873-2968 ISO Abbreviation: - Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-7-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier Inc. |
Affiliation:
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Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology. University of Tübingen, Wilhelmstrasse 56, D-72074 Tübingen, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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