The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids
Open accessAbstract
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.
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Citations
Cites
Endogenous Bile Acids Are Ligands for the Nuclear Receptor FXR/BAR
Wang, H., Chen, J., Hollister, K., Sowers, L. C., & Forman, B. M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80348-2 · Cited by 1,636
Cited by
The Enzymes, Regulation, and Genetics of Bile Acid Synthesis
Russell, D. W. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161712 · Cited by 2,069
Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation
Lefebvre, P., Cariou, B., Lien, F., Kuipers, F., & Staels, B. (2009) · Physiological Reviews · doi:10.1152/physrev.00010.2008 · Cited by 1,678
Bile acids: regulation of synthesis
Chiang, J. Y. L. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r900010-jlr200 · Cited by 1,515
Targeting bile‐acid signalling for metabolic diseases
Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J., & Schoonjans, K. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2619 · Cited by 1,422
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280
Metadata
- Authors
- Xie, W., Radominska-Pandya, A., Shi, Y., Simon, C. M., Nelson, M. C., Ong, E. S., Waxman, D. J., & Evans, R. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-03-13
- Volume
- 98
- Issue
- 6
- Pages
- 3375-3380
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2026160870
- Cited by
- 757
- References
- 1
- FWCI
- 20.90
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. https://app.cochat.ai/papers/10.1073/pnas.051014398
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- Xie, W., Radominska-Pandya, A., Shi, Y., Simon, C. M., Nelson, M. C., Ong, E. S., Waxman, D. J., & Evans, R. M. (2001). An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.051014398
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