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Coordinate regulation of hepatic bile acid oxidation and conjugation by nuclear receptors.
- Source :
-
Molecular pharmaceutics [Mol Pharm] 2006 May-Jun; Vol. 3 (3), pp. 212-22. - Publication Year :
- 2006
-
Abstract
- Bile acids play important functions in the maintenance of bile acid homeostasis. However, due to their detergent properties, these acids are inherently cytotoxic and their accumulation in liver is associated with hepatic disorders such as cholestasis. During their enterohepatic circulation, bile acids undergo several metabolic alterations, including amidation, hydroxylation, sulfonation, and glucuronidation. Most of these transformations facilitate the excretion of bile acids into the bile (amidation and sulfonation) or into the blood for subsequent urinary elimination (hydroxylation, sulfonation, and glucuronidation). In this review, the role of various nuclear receptors and transcription factors in the expression of bile acid detoxification enzymes is summarized. In particular, the coordinate manner in which the xenobiotic sensors pregnane X receptor and constitutive androstane receptor, the lipid sensors liver X receptor, farnesoid X receptor, peroxisome proliferator-activated receptor alpha, and vitamin D receptor, and the orphan receptors hepatocyte nuclear factor 4alpha and small heterodimer partner regulate bile acid detoxification is detailed. Finally, we conclude by discussing the importance of these transcription factors as promising drug targets for the correction of cholestasis.
- Subjects :
- Animals
Constitutive Androstane Receptor
DNA-Binding Proteins metabolism
Humans
Hydroxylation
Liver enzymology
Liver X Receptors
Metabolic Detoxication, Phase II
Mice
Models, Biological
Orphan Nuclear Receptors
Oxidation-Reduction
PPAR alpha metabolism
Pregnane X Receptor
Receptors, Calcitriol metabolism
Receptors, Steroid metabolism
Transcription Factors metabolism
Bile Acids and Salts metabolism
Receptors, Cytoplasmic and Nuclear metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1543-8384
- Volume :
- 3
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 16749854
- Full Text :
- https://doi.org/10.1021/mp060020t