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Liver X receptor regulates expression of MRP2 but not that of MDR1 and BCRP in the liver

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Title: Liver X receptor regulates expression of MRP2 but not that of MDR1 and BCRP in the liver
Authors: Chisaki, Ikumi Browse this author
Kobayashi, Masaki Browse this author →KAKEN DB
Itagaki, Shirou Browse this author
Hirano, Takeshi Browse this author
Iseki, Ken Browse this author
Keywords: Liver X receptor
ABC transporter
Regulation
Issue Date: Nov-2009
Publisher: Elsevier B.V.
Journal Title: Biochimica et Biophysica Acta (BBA) : Biomembranes
Volume: 1788
Issue: 11
Start Page: 2396
End Page: 2403
Publisher DOI: 10.1016/j.bbamem.2009.08.014
PMID: 19728987
Abstract: Liver X receptors (LXRs) belong to the nuclear hormone receptor superfamily. Multidrug resistance-associated protein 2 (MRP2), multidrug resistance 1 (MDR1) and breast cancer resistance protein (BCRP) play an important role in the efflux of a broad range of endogenous and xenobiotic compounds from hepatocytes. Since the effects of LXR activation on there transporters have been obscure, we investigated the effects of LXR agonists, TO901317 and 25-hydroxycholesterol, on MRP2, MDR1, BCRP expression in HepG2 cells and the rat liver. in an in vitro study, TO901317 increased ABCA1, an LXR target gene, and MRP2 mRNA and protein levels. On the other hand, TO901317 had little effect on MDR1 and BCRP mRNA levels. In an in vivo study, Abca1 and Mrp2 mRNA and protein levels were increased by TO901317. but TO901317 had no effect on Mdr1a and Bcrp mRNA levels in the rat liver. Moreover, TO901317-induced MRP2 mRNA expression was blocked by LXRα knockdown. In this study, we demonstrated that LXR activation induced expression of MRP2 but not that of MDR1 and BCRP in hepatocytes. The results suggest that agonists for LXR activate transcription of the MRP2 gene in order to promote excretion of endogenous and xenobiotic compounds from hepatocytes into bile.
Type: article (author version)
URI: http://hdl.handle.net/2115/39963
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 小林 正紀

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