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The Repressed Nuclear Receptor CAR Responds to Phenobarbital in Activating the Human CYP2B6 Gene*
TLDR
Activation of the repressed nuclear receptor CAR appears to be a versatile mediator that regulates PB induction of the CYP2B and other genes. Expand
The Nuclear Orphan Receptor CAR-Retinoid X Receptor Heterodimer Activates the Phenobarbital-Responsive Enhancer Module of the CYP2B Gene
TLDR
PBREM was synergistically activated by transfection of CAR and RXR in HepG2 and HEK293 cells when the NR1 site was functional and has thus been characterized as atrans-acting factor for the phenobarbital-inducibleCyp2b10 gene. Expand
Phenobarbital-Responsive Nuclear Translocation of the Receptor CAR in Induction of the CYP2B Gene
TLDR
Both immunoprecipitation and immunohistochemistry studies show cytoplasmic localization of CAR in the livers of nontreated mice, indicating that CAR translocates into nuclei following PB treatment. Expand
CAR and PXR: The xenobiotic-sensing receptors
The xenobiotic receptors CAR and PXR constitute two important members of the NR1I nuclear receptor family. They function as sensors of toxic byproducts derived from endogenous metabolism and ofExpand
Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital.
TLDR
Cyp4a10 and Cyp4a14 represented the group of genes induced by PB only in CAR-null mice, indicating that CAR may be a transcription blocker that prevents these genes from being induced or repressed by PB. Expand
Nuclear Receptors CAR and PXR Cross Talk with FOXO1 To Regulate Genes That Encode Drug-Metabolizing and Gluconeogenic Enzymes
TLDR
It is concluded that FOXO1 and the nuclear receptors reciprocally coregulate their target genes, modulating both drug metabolism and gluconeogenesis. Expand
Relative Activation of Human Pregnane X Receptor versus Constitutive Androstane Receptor Defines Distinct Classes of CYP2B6 and CYP3A4 Inducers
TLDR
It is demonstrated that CMZ, EFV, and NVP induce CYP2B6 and CYP3A4 preferentially through hCAR and that hCAR3 represents a sensitive tool for in vitro prediction of chemical-mediated human CAR activation. Expand
Phenobarbital response elements of cytochrome P450 genes and nuclear receptors.
TLDR
Phenobarbital response elements and NRs are functionally versatile, and capable of responding to distinct but overlapping groups of xenochemicals. Expand
A Novel Distal Enhancer Module Regulated by Pregnane X Receptor/Constitutive Androstane Receptor Is Essential for the Maximal Induction of CYP2B6 Gene Expression*
TLDR
Results show that a novel xenobiotic-responsive enhancer module in the distal region of the CYP2B6 promoter (CYP2B 6-XREM) together with the PBREM mediates optimal drug-induced expression ofCYP 2B6. Expand
The phenobarbital response enhancer module in the human bilirubin UDP‐glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR
TLDR
The UDP‐glucuronosyltransferase, UGT1A1, is the critical enzyme responsible for detoxification of the potentially neurotoxic bilirubin by conjugating it with glucuronic acid and was effectively activated in mouse primary hepatocytes in response to phenobarbital. Expand
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