Selective suppressions of human CYP3A forms, CYP3A5 and CYP3A7, by troglitazone in HepG2 cells.
Troglitazone is an insulin sensitizer and also known as an agonist of peroxisome proliferator-activated receptor-gamma (PPARgamma). In the present study, we have studied the influence of troglitazone on CYP3A form expressions in HepG2 cells for a model of human tissue. Interestingly, constitutively expressed forms of cytochrome P450, CYP3A5 and CYP3A7, were suppressed by the pretreatment of troglitazone but not of the related thiazolidinediones, pioglitazone and rosiglitazone in this cell line. A major liver CYP3A form, CYP3A4, was not detected in this cell line with and without troglitazone treatment. The troglitazone-mediated suppressions of CYP3A5 and CYP3A7 were found to be independent of expression levels of nuclear transcriptional factors, PXR, RXRalpha and PPARgamma. These results suggest that the selectively suppressive effects of troglitazone on CYP3A5 and CYP3A7 expressions may be caused by a novel pathway.
Ogino
Makoto
M
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Nagata
Kiyoshi
K
Yamazoe
Yasushi
Y