Reciprocal activation of Xenobiotic response genes by nuclear receptors SXR/PXR and CAR
Article Abstract:
Activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR is discussed. It is reciprocal. Observations of a recent study give a rational explanation for activation of multiple CYP gene classes by certain xenobiotics. They also show existence of a metabolic safety net. This puts a second layer of protection against the harmful effects of toxic compounds out. It also raises the propensity for interactions among drugs.
Publication Name: Genes & Development
Subject: Biological sciences
ISSN: 0890-9369
Year: 2000
User Contributions:
Comment about this article or add new information about this topic:
Orphan nuclear receptors - new ligands and new possibilities
Article Abstract:
Nuclear hormone receptors take in a large superfamily made up of ligand-modulated transcription factors. These to some degree mediate response to retinoids, steroids, and thyroid hormones. They also play roles in development and body physiology. Advances have been made on four novel orphan receptor-mediated signaling pathways: benzoate X receptor (BXR); constitutive androstane receptor (CAR beta); steroid and Xenobiotic receptor (SXR); and pregnane X receptor (PXR). There is some recent progress as well for PPAR gamma, FXR, and LXR alpha. Orphans that form heterodimers with RXR are of particular interest. There are new modes of regulation and there may be new drug targets. All orphans cannot be expected to be unidentified endocrine systems.
Publication Name: Genes & Development
Subject: Biological sciences
ISSN: 0890-9369
Year: 1998
User Contributions:
Comment about this article or add new information about this topic:
SXR, a novel steroid and xenobiotic-sensing nuclear receptor
Article Abstract:
Low-specificity sensing receptors may make up a novel branch of the superfamily of nuclear receptors. An important necessity for physiologic homeostasis is removal and detoxification of xenobiotic compounds and biologically active endogenous hormones. Much detoxification is carried out by cytochrome P-450 enzymes. Many of these enzymes have low substrate specificity and are inducible by a large number of different compounds, steroids among them. The existence of a few low-specificity, low-affinity sensing receptors that might monitor levels of inducers in the aggregate to start production of metabolizing enzymes has been proposed. A novel nuclear receptor, called the steroid and xenobiotic receptor (SXR) by the team that isolated it, gives evidence for the proposal. SXR activates transcription as a response to a variety of synthetic and naturally occuring compounds.
Publication Name: Genes & Development
Subject: Biological sciences
ISSN: 0890-9369
Year: 1998
User Contributions:
Comment about this article or add new information about this topic:
- Abstracts: Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
- Abstracts: Ligand-mediated negative regulation of a chimeric transmembrane receptor tyrosine phosphatase. Cell signaling by receptor tyrosine kinases
- Abstracts: Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors. Kinesin-dependent axonal transport is mediated by the sunday driver (SYD) protein
- Abstracts: Estimating quantitative genetic parameters in haplodiploid organisms. Local drift load and the heterosis of interconnected populations
- Abstracts: Macrogeographic patterns of breeding system diversity in the Daphnia pulex group from the United States and Mexico