Broad but Distinct Role of Pregnane X Receptor on the Expression of Individual Cytochrome P450s in Human Hepatocytes
作者： Koki Kojima , Kiyoshi Nagata , Tsutomu Matsubara , Yasushi Yamazoe
DOI: 10.2133/DMPK.22.276
关键词:
摘要: Summary: In the present study, we have utilized a target selective human pregnane X receptor-siRNA (hPXR-siRNA)-adenovirus expression system to examine contribution of hPXR on gene regulation drug-metabolizing P450s in hepatocytes. Introduction hPXR-siRNA adenoviral vector reduced level PXR mRNA. After infection with Ad hPXR-siRNA, basal and ligand-activated CYP2A6, CYP2C8, CYP3A4 CYP3A5 mRNA levels were decreased significantly dose-dependent manners, whereas CYP2B6, CYP2C9 CYP2C19 moderately influenced after hPXR-siRNA. These data suggest distinct influences these genes. The CYP1A2 CYP2D6 not affected by introduction suggesting that plays no functional role either This is first report compare simultaneously relative nine forms P450 primary cultured Mutual sharing among nuclear receptors their binding cis-elements becomes clear now. Thus, method using combination adenovirus-mediated hepatocytes may offer information such as drug metabolizing
sci-hub.se 参考文章(40)
Tsutomu Matsubara, Wachiraporn Noracharttiyapot, Takayoshi Toriyabe, Kouichi Yoshinari, Kiyoshi Nagata, Yasushi Yamazoe, None, Assessment of human pregnane X receptor involvement in pesticide-mediated activation of CYP3A4 gene. Drug Metabolism and Disposition. ,vol. 35, pp. 728- 733 ,(2007) , 10.1124/DMD.106.013144
B. Blumberg, W. Sabbagh Jr., H. Juguilon, J. Bolado Jr., C. M. van Meter, E. S. Ong, R. M. Evans, SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes & Development. ,vol. 12, pp. 3195- 3205 ,(1998) , 10.1101/GAD.12.20.3195
Stephen S. Ferguson, Yuping Chen, Edward L. LeCluyse, Masahiko Negishi, Joyce A. Goldstein, Human CYP2C8 Is Transcriptionally Regulated by the Nuclear Receptors Constitutive Androstane Receptor, Pregnane X Receptor, Glucocorticoid Receptor, and Hepatic Nuclear Factor 4α Molecular Pharmacology. ,vol. 68, pp. 747- 757 ,(2005) , 10.1124/MOL.105.013169
Yuping Chen, Stephen S. Ferguson, Masahiko Negishi, Joyce A. Goldstein, Identification of Constitutive Androstane Receptor and Glucocorticoid Receptor Binding Sites in the CYP2C19 Promoter Molecular Pharmacology. ,vol. 64, pp. 316- 324 ,(2003) , 10.1124/MOL.64.2.316
Thomas Langmann, Richard Mauerer, Alexandra Zahn, Christoph Moehle, Mario Probst, Wolfgang Stremmel, Gerd Schmitz, Real-Time Reverse Transcription-PCR Expression Profiling of the Complete Human ATP-Binding Cassette Transporter Superfamily in Various Tissues Clinical Chemistry. ,vol. 49, pp. 230- 238 ,(2003) , 10.1373/49.2.230
Takeshi Kawamoto, Tatsuya Sueyoshi, Igor Zelko, Rick Moore, Kimberly Washburn, Masahiko Negishi, Phenobarbital-Responsive Nuclear Translocation of the Receptor CAR in Induction of the CYP2B Gene Molecular and Cellular Biology. ,vol. 19, pp. 6318- 6322 ,(1999) , 10.1128/MCB.19.9.6318
Bryan Goodwin, Ecushla Hodgson, Christopher Liddle, The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Molecular Pharmacology. ,vol. 56, pp. 1329- 1339 ,(1999) , 10.1124/MOL.56.6.1329
Timothy W. Synold, Isabelle Dussault, Barry Marc Forman, The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nature Medicine. ,vol. 7, pp. 584- 590 ,(2001) , 10.1038/87912
Andrew Fire, SiQun Xu, Mary K. Montgomery, Steven A. Kostas, Samuel E. Driver, Craig C. Mello, Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans Nature. ,vol. 391, pp. 806- 811 ,(1998) , 10.1038/35888
Yasuna Kobayashi, Yoichi Matsuura, Eiichi Kotani, Teruo Fukuda, Takaaki Aoyagi, Seisho Tobinaga, Takemi Yoshida, Yukio Kuroiwa, Structural requirements for the induction of hepatic microsomal cytochrome P450 by imidazole- and pyridine-containing compounds in rats. Journal of Biochemistry. ,vol. 114, pp. 697- 701 ,(1993) , 10.1093/OXFORDJOURNALS.JBCHEM.A124239