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Induction of a distinct drug clearance program by a high-affinity ligand for the related nuclear receptor, the constitutive androstane receptor, does not overcome the lethality, indicating the unique requirement of PXR for detoxification. We propose that the PXR signaling pathway protects the body from toxic dietary cholesterol metabolites, and, by extension, PXR ligands may ameliorate human diseases such as cholestatic liver diseases and the associating acute renal failure.<\/jats:p>","DOI":"10.1073\/pnas.0409481102","type":"journal-article","created":{"date-parts":[[2005,1,25]],"date-time":"2005-01-25T22:43:38Z","timestamp":1106693018000},"page":"2198-2203","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":71,"title":["Pregnane X receptor prevents hepatorenal toxicity from cholesterol metabolites"],"prefix":"10.1073","volume":"102","author":[{"given":"Junichiro","family":"Sonoda","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute and Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA 94121; Molecular Pharmacology Laboratory, Westmead Millennium Institute, and Institute of Clinical Pathology and Medical Research, University of Sydney at Westmead Hospital, Westmead 2145, Australia; and Department of Genetics and Complex Diseases, Harvard School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling Wa","family":"Chong","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA 94121; Molecular Pharmacology Laboratory, Westmead Millennium Institute, and Institute of Clinical Pathology and Medical Research, University of Sydney at Westmead Hospital, Westmead 2145, Australia; and Department of Genetics and Complex Diseases, Harvard School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Downes","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA 94121; 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