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• W2035321503 endingPage "525" @default.
• W2035321503 startingPage "515" @default.
• W2035321503 abstract "The expression of the CAR gene is lost in most cultured cell lines, and exogenously expressed CAR accumulates spontaneously in the nuclear compartment, where CAR is constitutively active. Therefore, the assessment of CAR-dependent transcriptional activation has to be evaluated using either animal models or primary cultured hepatocytes. Furthermore, due to the species-specific response of CAR to individual compounds, the results obtained with animal models are not directly applicable to human cases. We established a novel screening system for hCAR ligands (including agonists and inverse agonists) by expressing GAL4/DBD-fused hCAR/LBD, in which three consecutive alanine residues were inserted between helix 11 and helix 12 of LBD, and a commercially obtained plasmid consisting of the firefly luciferase gene downstream of the GAL4 responsive element in a cultured cell line. Androstenol (Andro) and clotrimazole (CLT), which are both inverse agonists of hCAR, were classified as an antagonist and weak agonist, respectively, in our novel assay system. Among DDT and its metabolites DDE and DDD, only DDT worked as an agonist of the hCAR mutant, although all of them were enrolled as agonists of SXR. Using this system, the screening for hCAR ligands can be conducted without sacrificing animals." @default.
• W2035321503 created "2016-06-24" @default.
• W2035321503 creator A5052444820 @default.
• W2035321503 creator A5068398222 @default.
• W2035321503 date "2010-01-01" @default.
• W2035321503 modified "2023-10-05" @default.
• W2035321503 title "A consecutive three alanine residue insertion mutant of human CAR: a novel CAR ligand screening system in HepG2 cells" @default.
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• W2035321503 doi "https://doi.org/10.2131/jts.35.515" @default.
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