Induction of CYP3A4 by 1alpha,25-dyhydroxyvitamin D3 in HepG2 cells.
CYP3A4, the predominant cytochrome P450 (CYP) expressed in human liver, contributes to the metabolism of approximately half the drugs in use today. In general, human-derived cell lines fail to express CYPs. It was previously shown that CYP3A4 mRNA and CYP3A immunoreactive protein are induced by 1alpha,25-dyhydroxyvitamin D(3) (1alpha,25-(OH)(2)D(3)) in the human colon carcinoma cell line Caco-2. The aim of the present study was to examine whether 1alpha,25-(OH)(2)D(3) regulates CYP3A4 gene expression in HepG2 cells, a human hepatocarcinoma cell line. Treatment with 1alpha,25-(OH)(2)D(3) resulted in an induction of CYP3A4 mRNA and CYP3A4 immunoreactive protein, 1.5-fold and 4.0-fold respectively, when compared to control cultures, in a time-dependent fashion. These observations are in agreement with previous reports suggesting a role of 1alpha,25-(OH)(2)D(3) on CYP3A4 transcription regulation, and demonstrate that this hormone, as in Caco-2 cells, increase CYP3A4 levels in HepG2 cells. In conclusion, HepG2 cell cultures treated with 1alpha,25-(OH)(2)D(3), provides a useful model to study the function of CYP3A4 and its role in drug liver metabolism.
Sección Externa de Toxicología, CINVESTAV-IPN, P.O. Box 14-740, México, D.F. 07000, Mexico. gazuela@mail.cinvestav.mx
Guillermo
G
Elizondo
Irma M
IM
Medina-Díaz
D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D002117:Calcitriol