Back to Search
Start Over
SUMOylation of pregnane X receptor suppresses rifampicin-induced CYP3A4 and P-gp expression and activity in LS174T cells
SUMOylation of pregnane X receptor suppresses rifampicin-induced CYP3A4 and P-gp expression and activity in LS174T cells
- Source :
- Journal of Pharmacological Sciences, Vol 130, Iss 2, Pp 66-71 (2016)
- Publication Year :
- 2016
- Publisher :
- Elsevier, 2016.
-
Abstract
- The pregnane X receptor (PXR) has been well-established as a critical mediator in regulating important drug metabolizing enzymes and transporter proteins, including cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). Previous studies identified that PXR served as a molecular target of SUMOylation. However, the impact of SUMOylation of PXR on its transcriptional activity in regulating the expression/activity of the target genes is poorly investigated. In the current study, we established cell-based models of SUMOylated PXR in LS174T cells to investigate the impact of SUMOylation of PXR on regulating the expression/activity of CYP3A4 and P-gp. Our results revealed that rifampicin-induced PXR transactivation of the CYP3A4 and P-gp promoter was suppressed by SUMOylation of PXR in reporter gene assay. The mRNA and protein expression of CYP3A4 and P-gp was also suppressed. Moreover, CYP3A4 enzymatic assay and Rho123 intracellular assay revealed that rifampicin-induced CYP3A4 and P-gp activity was also suppressed by SUMOylated PXR. Our data collectively indicated for the first time that SUMOylation of PXR exerts suppressive effect on rifampicin-induced expression and activity of CYP3A4 and P-gp, which suggest that alteration in the SUMOylation status of PXR will be expected to affect the CYP3A4 mediated drug metabolism and P-gp mediated drug transport.
Details
- Language :
- English
- ISSN :
- 13478613
- Volume :
- 130
- Issue :
- 2
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Pharmacological Sciences
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.2acfb0aab0db439f8187e063a8372754
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.jphs.2015.11.006