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characterized activity profile of CAR and compared with hCAR (show CXADR Proteins) and mCAR (show CXADR Proteins); related this to structural homology among the 3 orthologues; 5 alternative splice variants identified and sequenced each of which generated a truncated protein product
CAR is important for hepatic clearance of several widely prescribed drugs metabolized by P450 (show POR Proteins) enzymes, however the fasting-induced (show C10orf10 Proteins) alterations in P450 (show POR Proteins)-mediated drug clearance are largely independent of CAR.
The present study has revealed known and novel, as well as common and unique targets of PXR (show NR1I2 Proteins) and CAR in mouse liver following pharmacological activation using their prototypical ligands.
Results show that circadian disruption activates CAR via sympathetic dysfunction and cholestasis. The nuclear receptor CAR drives NAFLD to NASH (show SAMSN1 Proteins), fibrosis, and hepatocellular carcinoma progression
data indicate that DE might be a potential therapeutic agent for obese pregnant patients with insulin (show INS Proteins) resistance through CAR to prevent the perinatal outcomes such as preeclampsia, gestational diabetes, and macrosomia. Further analysis of possible complications and side effects using animal models is required.
Combining CAR activation with limited beta-catenin (show CTNNB1 Proteins) activation induces tumorigenesis, and the tumours share a conserved gene expression signature with beta-catenin (show CTNNB1 Proteins)-positive human hepatocellular carcinoma.
Constitutive androstane receptor is the main mediator of liver hypertrophy induced by cyproconazole and fluconazole, but not tebuconazole; constitutive androstane receptor played a crucial role in liver tumor development induced by all three triazoles.
CAR activation decreases miR (show MLXIP Proteins)-122 levels through suppression of HNF4alpha (show HNF4A Proteins) transcriptional activity and indirectly regulates the promitogenic protein cMyc (show MYC Proteins).
The induction of CYP2B by PB or CFA (show TBCA Proteins) was comparable to nuclear CAR levels. CAR nuclear translocation was induced by CFA (show TBCA Proteins) in both rat strains.
The nuclear receptor constitutive androstane receptor/NR1I3 enhances the profibrotic effects of transforming growth factor beta and contributes to the development of experimental dermal fibrosis.
ubiquitin-proteasomal regulation of CCRP (show DNAJC7 Proteins) and HSP70 (show HSP70 Proteins) are important contributors to the regulation of cytoplasmic CAR levels, and hence the ability of CAR to respond to PB or PB-like inducers
Data suggest both PXR (show NR1I2 Proteins) and CAR are expressed in testis/Sertoli cells; exposure of Sertoli cells (in vitro model of blood-testis barrier) to PXR (show NR1I2 Proteins) or CAR ligands (including antiretroviral drugs) up-regulates expression of Pgp/ABCB1 (show ABCB4 Proteins), BCRP, and MRP4 (show ABCC4 Proteins). (PXR (show NR1I2 Proteins) = pregnane X receptor (show NR1I2 Proteins); CAR = constitutive androstane receptor; Pgp/ABCB1 (show ABCB4 Proteins) = P-glycoprotein ABCB1 (show ABCB1 Proteins); BCRP = breast cancer resistance protein; MRP4 (show ABCC4 Proteins) =multidrug resistance protein 4)
Genome-wide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR (show NR1I2 Proteins) and PPARalpha (show PPARA Proteins) in primary human hepatocytes has been presented.
Integrative analysis of four RNA-Seq datasets and differential expression revealed for the first time, splicing alterations of SLC39A14 (show SLC39A14 Proteins) and NR1I3 in hepatocellular carcinoma.
These results reveal both novel and known targets of hCAR (show CXADR Proteins) and support the role of hCAR (show CXADR Proteins) in maintaining the homeostasis of metabolism and cell proliferation in the liver.
Around 42.5% of the overall interindividual variability in warfarin dose requirements was explained : VKORC1 (show VKORC1 Proteins) genotype accounted for 29.6%, CYP2C9 (show CYP2C9 Proteins) genotype for 4.3%, age for 3.6%, the CYP4F2 genotype for 3.3%, and CAR/HNF4alpha (show HNF4A Proteins) (rs2501873/rs3212198) for 1.7%
It is suggested that the functions of PXR (show NR1I2 Proteins), CAR and AhR (show AHR Proteins) may be closely implicated in the pathogeneses of metabolic vascular diseases, such as hyperlipidemia, atherogenesis, and hypertension.
Suggest that PXR and CAR double humanized mice are more sensitive rifampcin induction of cytochrome P450 and UDP-glucuronosyltransferases.
PRMT5 (show PRMT5 Proteins) enhances transcriptional activity of constitutive androstane receptor.PRMT5 is a gene-selective co-activator for CAR.
Donor CYP3A5 (show CYP3A5 Proteins), NR1I3 gene polymorphisms.
This gene encodes a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and endobiotic metabolism. The protein binds to DNA as a monomer or a heterodimer with the retinoid X receptor and regulates the transcription of target genes involved in drug metabolism and bilirubin clearance, such as cytochrome P450 family members. Unlike most nuclear receptors, this transcriptional regulator is constitutively active in the absence of ligand but is regulated by both agonists and inverse agonists. Ligand binding results in translocation of this protein to the nucleus, where it activates or represses target gene transcription. These ligands include bilirubin, a variety of foreign compounds, steroid hormones, and prescription drugs. Multiple transcript variants encoding different isoforms have been found for this gene.
constitutive androstane receptor
, constitutively transactivates RAREs
, nuclear receptor subfamily 1 group I member 3
, orphan nuclear receptor MB67
, constitutive androstane receptor NR1I3
, nuclear receptor constitutive active receptor
, strain Fischer nuclear receptor (CAR)
, constitutive activator of retinoid response
, constitutive active receptor
, constitutive active response
, constitutive androstane nuclear receptor variant 2
, constitutive androstane nuclear receptor variant 3
, constitutive androstane nuclear receptor variant 4
, constitutive androstane nuclear receptor variant 5
, orphan nuclear hormone receptor
, xenobiotic receptor