Regulation of a xenobiotic sulfonation cascade by nuclear pregnane X receptor (PXR)
Autor: | Wen Xie, Ronald M. Evans, Joyce L. Barwick, Philip S. Guzelian, John M. Rosenfeld, Junichiro Sonoda |
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Rok vydání: | 2002 |
Předmět: |
Receptors
Steroid Lithocholic acid Receptors Cytoplasmic and Nuclear Mice Transgenic Biology Xenobiotics Mice chemistry.chemical_compound Sulfation Detoxification Constitutive androstane receptor Animals Humans Mice Knockout chemistry.chemical_classification Pregnane X receptor Multidisciplinary Sulfates Pregnane X Receptor Biological Sciences Recombinant Proteins Rats Enzyme Liver Biochemistry Nuclear receptor chemistry Hepatocytes Lithocholic Acid Sulfotransferases Xenobiotic |
Zdroj: | Proceedings of the National Academy of Sciences. 99:13801-13806 |
ISSN: | 1091-6490 0027-8424 |
Popis: | The nuclear receptor PXR (pregnane X receptor) protects the body from hepatotoxicity of secondary bile acids such as lithocholic acid (LCA) by inducing expression of the hydroxylating cytochrome P450 enzyme CYP3A and promoting detoxification. We found that activation of PXR also increases the activity and gene expression of the phase II conjugating enzyme dehydroepiandrosterone sulfotransferase (STD) known to sulfate LCA to facilitate its elimination. This activation is direct and appears to extend to other xenobiotic sulfotransferases as well as to 3′-phosphoadenosine 5′-phosphosulfate synthetase 2 (PAPSS2), an enzyme that generates the donor cofactor for the reaction. Because sulfation plays an important role in the metabolism of many xenobiotics, prescription drugs, and toxins, we propose that PXR serves as a master regulator of the phase I and II responses to facilitate rapid and efficient detoxification and elimination of foreign chemicals. |
Databáze: | OpenAIRE |
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