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• W2022136199 abstract "In an assay system using a human CYP3A4 reporter constructed with the promoter (+ 11 nt to − 362 nt) and enhancer (− 7.2 knt to − 7.8 knt) regions including everted repeat separated by six nucleotides (ER-6) and direct repeat separated by three nucleotides (DR-3) motifs, the CYP3A4 transactivation was detected without overexpression of any nuclear receptors in rifampicin-treated HepG2 cells. Overexpression of human pregnane X receptor (hPXR) enhanced the transactivation. Rat CYP3A1 reporter constructed with the promoter region (+ 31 nt to − 171 nt) including both DR-3 and ER-6 motifs was, however, not transactivated in rifampicin-treated cells, even after overexpression of hPXR. Although overexpression of retinoid X receptor alpha (RXRα) had no clear effect for both CYP3A reporters, co-expression of apolipoprotein AI regulatory protein-1 (ARP-1) with hPXR resulted in the rifampicin-induced transactivation of the CYP3A1 reporter. A truncated CYP3A4 reporter retaining the both motifs showed the rifampicin-induced transactivation by overexpression of hPXR and ARP-1, while the transactivation in hPXR-overexpressed cells was not observed. These results support the idea that a nuclear receptor other than RXRα may play a role in the CYP3A transactivation together with hPXR. The present study also suggests the involvement of a novel cis-element in the hPXR-mediated CYP3A4 transactivation." @default.
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• W2022136199 date "2004-01-01" @default.
• W2022136199 modified "2023-10-10" @default.
• W2022136199 title "Differences in Transactivation between Rat CYP3A1 and Human CYP3A4 Genes by Human Pregnane X Receptor" @default.
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• W2022136199 doi "https://doi.org/10.2133/dmpk.19.103" @default.
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