Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor
The nuclear pregnane X receptor (PXR; NR1I2) is an integral component of the body's defense mechanism against chemical insult (chemoprotection). PXR is activated by a diverse array of lipophilic chemicals, including xenobiotics and endogenous substances, and regulates the expression of cytochro...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2002-03-01
|
Series: | Journal of Lipid Research |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520301413 |
id |
doaj-9f051660ec5748cb8b053266ca2724c1 |
---|---|
record_format |
Article |
spelling |
doaj-9f051660ec5748cb8b053266ca2724c12021-04-27T04:38:12ZengElsevierJournal of Lipid Research0022-22752002-03-01433359364Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptorSteven A. Kliewer0Timothy M. Willson1To whom correspondence should be addressed.; Nuclear Receptor Discovery Research, GlaxoSmithKline, 5 Moore Drive, Room V118.1B, Research Triangle Park, NC 27709Nuclear Receptor Discovery Research, GlaxoSmithKline, 5 Moore Drive, Room V118.1B, Research Triangle Park, NC 27709The nuclear pregnane X receptor (PXR; NR1I2) is an integral component of the body's defense mechanism against chemical insult (chemoprotection). PXR is activated by a diverse array of lipophilic chemicals, including xenobiotics and endogenous substances, and regulates the expression of cytochromes P450, conjugating enzymes, and transporters involved in the metabolism and elimination of these potentially harmful chemicals from the body. Among the chemicals that bind and activate PXR is the toxic bile acid lithocholic acid; activation of PXR, in turn, protects against the severe liver damage caused by this bile acid. Thus, PXR serves as a physiological sensor of lithocholic acid and perhaps other bile acids and coordinately regulates genes involved in their detoxification. Interestingly, both the antibiotic rifampicin and the herbal antidepressant St. John's wort activate PXR and have anticholestatic properties, which suggests that more potent, selective PXR agonists may be useful in the treatment of biliary cholestasis or other diseases characterized by the accumulation of bile acids or other toxins in the liver. —Kliewer, S. A., and T. M. Willson. Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor.http://www.sciencedirect.com/science/article/pii/S0022227520301413nuclear receptorcytochrome P450lithocholic acidfarnesoid X receptorcholestasisdrug-drug interaction |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Steven A. Kliewer Timothy M. Willson |
spellingShingle |
Steven A. Kliewer Timothy M. Willson Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor Journal of Lipid Research nuclear receptor cytochrome P450 lithocholic acid farnesoid X receptor cholestasis drug-drug interaction |
author_facet |
Steven A. Kliewer Timothy M. Willson |
author_sort |
Steven A. Kliewer |
title |
Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor |
title_short |
Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor |
title_full |
Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor |
title_fullStr |
Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor |
title_full_unstemmed |
Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor |
title_sort |
regulation of xenobiotic and bile acid metabolism by the nuclear pregnane x receptor |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2002-03-01 |
description |
The nuclear pregnane X receptor (PXR; NR1I2) is an integral component of the body's defense mechanism against chemical insult (chemoprotection). PXR is activated by a diverse array of lipophilic chemicals, including xenobiotics and endogenous substances, and regulates the expression of cytochromes P450, conjugating enzymes, and transporters involved in the metabolism and elimination of these potentially harmful chemicals from the body. Among the chemicals that bind and activate PXR is the toxic bile acid lithocholic acid; activation of PXR, in turn, protects against the severe liver damage caused by this bile acid. Thus, PXR serves as a physiological sensor of lithocholic acid and perhaps other bile acids and coordinately regulates genes involved in their detoxification. Interestingly, both the antibiotic rifampicin and the herbal antidepressant St. John's wort activate PXR and have anticholestatic properties, which suggests that more potent, selective PXR agonists may be useful in the treatment of biliary cholestasis or other diseases characterized by the accumulation of bile acids or other toxins in the liver. —Kliewer, S. A., and T. M. Willson. Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor. |
topic |
nuclear receptor cytochrome P450 lithocholic acid farnesoid X receptor cholestasis drug-drug interaction |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520301413 |
work_keys_str_mv |
AT stevenakliewer regulationofxenobioticandbileacidmetabolismbythenuclearpregnanexreceptor AT timothymwillson regulationofxenobioticandbileacidmetabolismbythenuclearpregnanexreceptor |
_version_ |
1721507048285274112 |