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characterized activity profile of CAR and compared with hCAR (zeige CXADR Proteine) and mCAR (zeige CXADR Proteine); related this to structural homology among the 3 orthologues; 5 alternative splice variants identified and sequenced each of which generated a truncated protein product
The role of the CAR signaling pathways within testis was validated using specific CAR agonist (TCPOBOP) and inverse agonist (androstanol) that respectively inhibited or reproduced the phenotype observed in Fxralpha (zeige NR1H4 Proteine)-/- males fed Bile acids (BAs)-diet. These data open interesting perspectives to better define how BA homeostasis contributes to physiological or pathophysiological conditions via the modulation of CAR activity.
FXR (zeige NR1H4 Proteine) signaling is a bile acid nuclear receptor that regulates lipids and glucose homeostasis and lack of it causes hepatomegaly and liver dysfunction.
These results revealed the bilirubin transport regulatory mechanisms and highlighted the importance of CAR in modulating the bilirubin clearance pathway in the ALD mouse model.
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 (zeige FNDC5 Proteine) mRNA expression in the liver.
CAR is important for hepatic clearance of several widely prescribed drugs metabolized by P450 (zeige POR Proteine) enzymes, however the fasting-induced (zeige C10orf10 Proteine) alterations in P450 (zeige POR Proteine)-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 (zeige NR1I2 Proteine) 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 (zeige SAMSN1 Proteine), fibrosis, and hepatocellular carcinoma progression
data indicate that DE might be a potential therapeutic agent for obese pregnant patients with insulin (zeige INS Proteine) 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 (zeige CTNNB1 Proteine) activation induces tumorigenesis, and the tumours share a conserved gene expression signature with beta-catenin (zeige CTNNB1 Proteine)-positive human hepatocellular carcinoma.
Results suggest that TRIM24 (zeige TRIM24 Proteine) is a novel coactivator of the CAR that is involved in cell- and/or promoter- selective transactivation.
An overview of NR1I2 (zeige NR1I2 Proteine) and NR1I3 pharmacogenetic studies in various therapeutic fields.
replication confirmed at genome-wide significance the association of loci at FOXE1 with hypothyroidism, and PDE8B, CAPZB and PDE10A with serum TSH. A total of 12 SNPs seemed to explain nearly 7% of the serum TSH variation
Dual ligands of CAR/PXR (zeige NR1I2 Proteine) show distinct gene regulation patterns by regulating cross-talk between CAR and PXR (zeige NR1I2 Proteine).
Data suggest both PXR (zeige NR1I2 Proteine) and CAR are expressed in testis/Sertoli cells; exposure of Sertoli cells (in vitro model of blood-testis barrier) to PXR (zeige NR1I2 Proteine) or CAR ligands (including antiretroviral drugs) up-regulates expression of Pgp/ABCB1 (zeige ABCB4 Proteine), BCRP, and MRP4 (zeige ABCC4 Proteine). (PXR (zeige NR1I2 Proteine) = pregnane X receptor (zeige NR1I2 Proteine); CAR = constitutive androstane receptor; Pgp/ABCB1 (zeige ABCB4 Proteine) = P-glycoprotein ABCB1 (zeige ABCB1 Proteine); BCRP = breast cancer resistance protein; MRP4 (zeige ABCC4 Proteine) =multidrug resistance protein 4)
Genome-wide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR (zeige NR1I2 Proteine) and PPARalpha (zeige PPARA Proteine) 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 (zeige SLC39A14 Proteine) and NR1I3 in hepatocellular carcinoma.
These results reveal both novel and known targets of hCAR (zeige CXADR Proteine) and support the role of hCAR (zeige CXADR Proteine) 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 (zeige VKORC1 Proteine) genotype accounted for 29.6%, CYP2C9 (zeige CYP2C9 Proteine) genotype for 4.3%, age for 3.6%, the CYP4F2 genotype for 3.3%, and CAR/HNF4alpha (zeige HNF4A Proteine) (rs2501873/rs3212198) for 1.7%
It is suggested that the functions of PXR (zeige NR1I2 Proteine), CAR and AhR (zeige AHR Proteine) may be closely implicated in the pathogeneses of metabolic vascular diseases, such as hyperlipidemia, atherogenesis, and hypertension.
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