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Ligand dependent hepatic gene expression profiles of nuclear receptors CAR and PXR.
- Source :
-
Toxicology letters [Toxicol Lett] 2012 Aug 03; Vol. 212 (3), pp. 288-97. Date of Electronic Publication: 2012 Jun 12. - Publication Year :
- 2012
-
Abstract
- Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are key regulators of drug-metabolizing enzymes and transporters. These two receptors are closely associated with each other and also have overlapping functions. This study investigated the overall hepatic gene expression profiles and the regulatory roles of these nuclear receptors using CAR/PXR single and double knockout mice. Basal and ligand-stimulated gene expression profiles were obtained in each mouse using cDNA microarrays and a reverse transcriptase-polymerase chain reaction. Enzymes such as Cyp2b10, Cyp3a11, Cdc20 and Cdk1 displayed both CAR- and PXR-dependent induction. Inversely, enzymes such as Cyp4a10, Fos and Mme displayed both CAR- and PXR-dependent repression. Enzymes such as Cyp1a1, Cyp1a2 and c-Myc represented the group of genes only induced by CAR. Enzymes such as Aacs represented the group of genes induced only by the PXR. CAR and PXR are closely associated and have diverse roles, both as positive and negative regulators of hepatic genes including xenobiotic metabolism, apoptosis, cholesterol biosynthesis, lipid metabolism, and cytokine signaling pathways.<br /> (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Constitutive Androstane Receptor
Cytochrome P-450 Enzyme System biosynthesis
Cytochrome P-450 Enzyme System genetics
Gene Expression Profiling
Mice
Mice, Inbred C57BL
Mice, Knockout
Pregnane X Receptor
Protein Binding
Pyridines pharmacology
Receptors, Cytoplasmic and Nuclear metabolism
Receptors, Steroid metabolism
Reverse Transcriptase Polymerase Chain Reaction
Enzyme Induction genetics
Gene Expression Regulation, Enzymologic
Liver metabolism
Receptors, Cytoplasmic and Nuclear genetics
Receptors, Steroid genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3169
- Volume :
- 212
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 22698814
- Full Text :
- https://doi.org/10.1016/j.toxlet.2012.06.001