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Coordinate transcriptional regulation of transport and metabolism.
- Source :
-
Methods in enzymology [Methods Enzymol] 2005; Vol. 400, pp. 511-30. - Publication Year :
- 2005
-
Abstract
- Intestinal absorption and hepatic clearance of drugs, xenobiotics, and bile acids are mediated by transporter proteins expressed at the plasma membranes of intestinal epithelial cells and liver parenchymal cells in a polarized manner. Within enterocytes and hepatocytes, these exogenous or endogenous, potentially toxic compounds may be metabolized by phase I cytochrome P450 (CYP) and phase II conjugating enzymes. Many transporter proteins and metabolizing enzymes are subject to direct translational modification, enabling very rapid changes in their activity. However, to achieve intermediate and longer term changes in transport and enzyme activities, the genes encoding drug and bile acid transporters, as well as the CYP and conjugating enzymes, are regulated by a complex network of transcriptional cascades. These are typically mediated by specific members of the nuclear receptor family of transcription factors, particularly FXR, SHP, PXR, CAR, and HNF-4alpha. Most nuclear receptors are activated by specific ligands, including numerous xenobiotics (PXR, CAR) and bile acids (FXR). The fine-tuning of transcriptional control of drug and bile acid homeostasis depends on regulated interactions of specific nuclear receptors with their target genes.
- Subjects :
- Bile Acids and Salts metabolism
Bile Acids and Salts pharmacology
Humans
Inactivation, Metabolic
Receptors, Cytoplasmic and Nuclear drug effects
Xenobiotics pharmacology
Membrane Transport Proteins metabolism
Receptors, Cytoplasmic and Nuclear genetics
Receptors, Cytoplasmic and Nuclear metabolism
Transcriptional Activation
Subjects
Details
- Language :
- English
- ISSN :
- 0076-6879
- Volume :
- 400
- Database :
- MEDLINE
- Journal :
- Methods in enzymology
- Publication Type :
- Academic Journal
- Accession number :
- 16399367
- Full Text :
- https://doi.org/10.1016/S0076-6879(05)00028-5