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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Radominska-pandya, A. Nelson, M. C. Shi, Y. Simon, C. M. Evans, R. M. Xie, W. Waxman, D. J. Ong, E. S. |
| Description | Author Affiliation: Xie W ( Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.); |
| Abstract | Hepatic hydroxylation is an essential step in the metabolism and excretion of bile acids and is necessary to avoid pathologic conditions such as cholestasis and liver damage. In this report, we demonstrate that the human xenobiotic receptor SXR (steroid and xenobiotic receptor) and its rodent homolog PXR (pregnane X receptor) serve as functional bile acid receptors in both cultured cells and animals. In particular, the secondary bile acid derivative lithocholic acid (LCA) is highly hepatotoxic and, as we show here, a metabolic substrate for CYP3A hydroxylation. By using combinations of knockout and transgenic animals, we show that activation of SXR/PXR is necessary and sufficient to both induce CYP3A enzymes and confer resistance to toxicity by LCA, as well as other xenotoxicants such as tribromoethanol and zoxazolamine. Therefore, we establish SXR and PXR as bile acid receptors and a role for the xenobiotic response in the detoxification of bile acids. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 6 |
| Volume Number | 98 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2001-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Aryl Hydrocarbon Hydroxylases Bile Acids And Salts Metabolism Cholestasis Receptors, Cytoplasmic And Nuclear Physiology Receptors, Steroid Animals Cell Line Cell Nucleus Cercopithecus Aethiops Pathology Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System Enzyme Induction Lithocholic Acid Administration & Dosage Mice Mice, Knockout Oxidoreductases, N-Demethylating Substrate Specificity Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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