Intestinal cell-specific vitamin D receptor (VDR)-mediated transcriptional regulation of CYP3A4 gene

Petr Pavek , Katerina Pospechova , Lucie Svecova , Zdenka Syrova , Lucie Stejskalova , Jana Blazkova , Zdenek Dvorak , Jaroslav Blahos

CYP3A4 is the most important drug-metabolizing enzyme that is involved in biotransformation of more than 50% of drugs. Pregnane X receptor (PXR) dominantly controls CYP3A4 inducibility in the liver, whereas vitamin D receptor (VDR) transactivates CYP3A4 in the intestine by secondary bile acids. Four major functional PXR-binding response elements of CYP3A4 have been discovered and their cooperation was found to be crucial for maximal up-regulation of the gene in hepatocytes. VDR and PXR recognize similar response element motifs and share DR3(XREM) and proximal ER6 (prER6) response elements of the CYP3A4 gene.

Mots clés: CAR; eNR3A4; ER6; prER6; DR4; PXR; RE; qRT-PCR; RXRα; VDR; XREM; CLEM4; 25OHvitD; LCA; CDCA; EMSA; ChIP; pharmacokinetics; metabolism; cytochrome P450; CYP3A4; transcriptional regulation; nuclear receptors

Petr Pavek, Katerina Pospechova, Lucie Svecova, Zdenka Syrova, Lucie Stejskalova, et al.. Intestinal cell-specific vitamin D receptor (VDR)-mediated transcriptional regulation of CYP3A4 gene. Biochemical Pharmacology, 2009, 79 (2), pp.277. ⟨10.1016/j.bcp.2009.08.017⟩. ⟨hal-00535827⟩