SUMOylation of pregnane X receptor suppresses rifampicin-induced CYP3A4 and P-gp expression and activity in LS174T cells

Journal of Pharmacological Sciences
Huasen TanHuichang Bi

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 th...Continue Reading

References

Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·F ThiebautM C Willingham
Jan 9, 1998·Drug Metabolism Reviews·E T Morgan
Feb 15, 2001·Molecular Cell Biology Research Communications : MCBRC·W TangM Piquette-Miller
May 22, 2001·International Immunopharmacology·G HartmannM Piquette-Miller
Mar 15, 2005·Toxicology Letters·David BalayssacFrançois Coudore
Dec 2, 2008·Biochemical and Biophysical Research Communications·Eun Ju HwangKeun Il Kim
Jun 16, 2009·Cellular and Molecular Life Sciences : CMLS·Miia M RytinkiJorma J Palvimo
Jan 5, 2010·Toxicology and Applied Pharmacology·Lei ZhangShiew-Mei Huang
Aug 20, 2010·The Journal of Pharmacology and Experimental Therapeutics·Gang HuJeff L Staudinger
Mar 15, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jeff L StaudingerSridhar Mani
Mar 23, 2011·Drug Metabolism and Pharmacokinetics·Ling HuangMin Huang
Mar 13, 2014·PloS One·Cornelia J GeertsAlexander J A Groffen

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Citations

Feb 12, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yufei HeChangxiao Liu
Dec 11, 2019·Expert Opinion on Drug Metabolism & Toxicology·Teruo MurakamiNicholas Bodor
May 24, 2017·Amino Acids·Liuqin HeYulong Yin

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