Regular ArticleDifferences in Transactivation between Rat CYP3A1 and Human CYP3A4 Genes by Human Pregnane X Receptor
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A CAR-responsive enhancer element locating approximately 31 kb upstream in the 5'-flanking region of rat cytochrome P450 (CYP) 3A1 gene
2015, Drug Metabolism and PharmacokineticsCitation Excerpt :CAR responsive elements in the human genome have been reported, i.e., ER8 located at around −530 from CYP1A1 [27] and a DR5 motif located approximately −8 kb above ABCG2 [28]. Although overexpression of RXRα had no clear effect on the rCYP3A1 promoter (+31 to −171) including both DR3 and ER6 motifs, co-expression of apolipoprotein AI regulatory protein-1 with PXR resulted in a rifampicin-induced transactivation of the rat CYP3A1 promoter [29]. Compared to these reported NR responsive elements, this novel rCAR-dependent transcription regulator that we report here is far from the transcription initiation site of rCYP3A1 and does not require ligand activation, and transactivation activity is surprisingly strong.
Hepatocyte nuclear factor 6 activates the transcription of CYP3A4 in hepatocyte-like cells differentiated from human induced pluripotent stem cells
2013, Drug Metabolism and PharmacokineticsLower expression of HNF4α and PGC1α might impair rifampicin-mediated CYP3A4 induction under Conditions Where PXR is overexpressed in human fetal liver cells
2012, Drug Metabolism and PharmacokineticsPolycyclic aromatic hydrocarbons activate CYP3A4 gene transcription through human pregnane X receptor
2012, Drug Metabolism and PharmacokineticsHuman arylacetamide deacetylase is responsible for deacetylation of rifamycins: Rifampicin, rifabutin, and rifapentine
2011, Biochemical PharmacologyCitation Excerpt :After 24 h incubation, transfection was performed using Tfx-20 reagent (Promega, Madison, MI) as follows: The transfection mixtures consisted of 290 ng of pCYP3A4-362-7.7K and 10 ng of phRL-TK plasmid (Promega). The reporter construct pCYP3A4-362-7.7K contained the promoter region (−362 to −11) including the ER6 (everted repeat separated by six nucleotides) motif and the distal enhancer region (−7836 to −7200) including the DR3 (direct repeat separated by three nucleotides) motif of the CYP3A4 gene, to which PXR binds [24]. After 24 h incubation, the cells were treated with 0–20 μM rifamycins or their 25-deacetylmetabolites for 48 h, and the cells were harvested and lysed to measure the luciferase activity using a Dual Luciferase Reporter Assay System (Promega).
Post-transcriptional regulation of human pregnane X receptor by micro-RNA affects the expression of cytochrome P450 3A4
2008, Journal of Biological ChemistryCitation Excerpt :Then total RNA and nuclear extract were isolated. Evaluation of the Expression Level of PXR in HepG2 Using Reporter Construct Containing PXR-responsive Element—The reporter construct pCYP3A4-362-7.7K contains the promoter region (–362 to +11), including the ER6 (everted repeat separated by six nucleotides) motif and the distal enhancer region (–7836 to –7200), including the DR3 (direct repeat separated by three nucleotides) motif of the CYP3A4 gene, to which PXR binds (21). The day before transfection, HepG2 cells were seeded into 24-well plates.