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characterized activity profile of CAR and compared with hCAR (show CXADR Antibodies) and mCAR (show CXADR Antibodies); related this to structural homology among the 3 orthologues; 5 alternative splice variants identified and sequenced each of which generated a truncated protein product
Activation of constitutive androstane receptor results in maintained biliary excretion of bile acids despite a marked decrease of bile acids in liver.
Activation of the nuclear receptor constitutive androstane receptor (CAR) induced FNDC5 (show FNDC5 Antibodies) mRNA expression in the liver.
CAR is important for hepatic clearance of several widely prescribed drugs metabolized by P450 (show POR Antibodies) enzymes, however the fasting-induced alterations in P450 (show POR Antibodies)-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 Antibodies) 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 (show TSC2 Antibodies) to NASH (show SAMSN1 Antibodies), fibrosis, and hepatocellular carcinoma progression
data indicate that DE might be a potential therapeutic agent for obese pregnant patients with insulin (show INS Antibodies) 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 Antibodies) activation induces tumorigenesis, and the tumours share a conserved gene expression signature with beta-catenin (show CTNNB1 Antibodies)-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 Antibodies)-122 levels through suppression of HNF4alpha (show HNF4A Antibodies) transcriptional activity and indirectly regulates the promitogenic protein cMyc (show MYC Antibodies).
The induction of CYP2B by PB or CFA (show TBCA Antibodies) was comparable to nuclear CAR levels. CAR nuclear translocation was induced by CFA (show TBCA Antibodies) in both rat strains.
Data suggest both PXR (show NR1I2 Antibodies) and CAR are expressed in testis (show XKR3 Antibodies)/Sertoli cells; exposure of Sertoli cells (in vitro model of blood-testis barrier) to PXR (show NR1I2 Antibodies) or CAR ligands (including antiretroviral drugs) up-regulates expression of Pgp/ABCB1 (show ABCB4 Antibodies), BCRP (show ABCG2 Antibodies), and MRP4 (show ABCC4 Antibodies). (PXR (show NR1I2 Antibodies) = pregnane X receptor (show NR1I2 Antibodies); CAR = constitutive androstane receptor; Pgp/ABCB1 (show ABCB4 Antibodies) = P-glycoprotein ABCB1 (show ABCB1 Antibodies); BCRP (show ABCG2 Antibodies) = breast cancer resistance protein (show ABCG2 Antibodies); MRP4 (show ABCC4 Antibodies) =multidrug resistance protein 4)
Genome-wide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR (show NR1I2 Antibodies) and PPARalpha (show PPARA Antibodies) 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 Antibodies) and NR1I3 in hepatocellular carcinoma.
These results reveal both novel and known targets of hCAR (show CXADR Antibodies) and support the role of hCAR (show CXADR Antibodies) 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 Antibodies) genotype accounted for 29.6%, CYP2C9 (show CYP2C9 Antibodies) genotype for 4.3%, age for 3.6%, the CYP4F2 (show CYP4F2 Antibodies) genotype for 3.3%, and CAR/HNF4alpha (show HNF4A Antibodies) (rs2501873/rs3212198) for 1.7%
It is suggested that the functions of PXR (show NR1I2 Antibodies), CAR and AhR (show AHR Antibodies) may be closely implicated in the pathogeneses of metabolic vascular diseases, such as hyperlipidemia, atherogenesis, and hypertension.
Suggest that PXR (show NR1I2 Antibodies) and CAR double humanized mice are more sensitive rifampcin induction of cytochrome P450 (show CYP Antibodies) and UDP-glucuronosyltransferases.
PRMT5 (show PRMT5 Antibodies) enhances transcriptional activity of constitutive androstane receptor.PRMT5 is a gene-selective co-activator for CAR.
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.
Donor CYP3A5 (show CYP3A5 Antibodies), 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