Identification of the novel splicing variants for the hPXR in human livers - PubMed (original) (raw)
Identification of the novel splicing variants for the hPXR in human livers
Shuichi Fukuen et al. Biochem Biophys Res Commun. 2002.
Abstract
The human pregnane X receptor (hPXR) plays a key role in the regulation of both drug metabolism and efflux by inducing the expression of CYP3A4 and MDR1 gene. Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, we identified seven novel splicing variants of hPXR in tissue from a single human liver. The expression of hPXR-related transcripts in the liver samples of 15 Caucasian individuals was subsequently determined by RT-PCR assays. The pattern of expression levels of these transcripts varied among liver samples. These results suggest that the hPXR is expressed as several different transcripts in liver tissues, apparently due to alternative as well as defective gene splicing. Furthermore, because this study provides the possibility of interindividual differences in hPXR transcript profiles, these alternative splicings for hPXR may largely contribute to the interindividual variability in CYP3A4 and P-glycoprotein induction.
Similar articles
- Human PXR variants and their differential effects on the regulation of human UDP-glucuronosyltransferase gene expression.
Gardner-Stephen D, Heydel JM, Goyal A, Lu Y, Xie W, Lindblom T, Mackenzie P, Radominska-Pandya A. Gardner-Stephen D, et al. Drug Metab Dispos. 2004 Mar;32(3):340-7. doi: 10.1124/dmd.32.3.340. Drug Metab Dispos. 2004. PMID: 14977869 Free PMC article. - Protein phosphatase 2Cbetal regulates human pregnane X receptor-mediated CYP3A4 gene expression in HepG2 liver carcinoma cells.
Pondugula SR, Tong AA, Wu J, Cui J, Chen T. Pondugula SR, et al. Drug Metab Dispos. 2010 Sep;38(9):1411-6. doi: 10.1124/dmd.110.032128. Epub 2010 Jun 10. Drug Metab Dispos. 2010. PMID: 20538721 Free PMC article. - PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators.
Lamba V, Yasuda K, Lamba JK, Assem M, Davila J, Strom S, Schuetz EG. Lamba V, et al. Toxicol Appl Pharmacol. 2004 Sep 15;199(3):251-65. doi: 10.1016/j.taap.2003.12.027. Toxicol Appl Pharmacol. 2004. PMID: 15364541 - Differential regulation of hepatic CYP2B6 and CYP3A4 genes by constitutive androstane receptor but not pregnane X receptor.
Faucette SR, Sueyoshi T, Smith CM, Negishi M, Lecluyse EL, Wang H. Faucette SR, et al. J Pharmacol Exp Ther. 2006 Jun;317(3):1200-9. doi: 10.1124/jpet.105.098160. Epub 2006 Mar 2. J Pharmacol Exp Ther. 2006. PMID: 16513849 - A concise review on hPXR ligand-recognizing residues and structure-based strategies to alleviate hPXR transactivation risk.
Liu T, Beck JP, Hao J. Liu T, et al. RSC Med Chem. 2022 Jan 19;13(2):129-137. doi: 10.1039/d1md00348h. eCollection 2022 Feb 23. RSC Med Chem. 2022. PMID: 35308029 Free PMC article. Review.
Cited by
- The major human pregnane X receptor (PXR) splice variant, PXR.2, exhibits significantly diminished ligand-activated transcriptional regulation.
Lin YS, Yasuda K, Assem M, Cline C, Barber J, Li CW, Kholodovych V, Ai N, Chen JD, Welsh WJ, Ekins S, Schuetz EG. Lin YS, et al. Drug Metab Dispos. 2009 Jun;37(6):1295-304. doi: 10.1124/dmd.108.025213. Epub 2009 Feb 27. Drug Metab Dispos. 2009. PMID: 19251824 Free PMC article. - Comparative genomics of xenobiotic metabolism: a porcine-human PXR gene comparison.
Pollock CB, Rogatcheva MB, Schook LB. Pollock CB, et al. Mamm Genome. 2007 Mar;18(3):210-9. doi: 10.1007/s00335-007-9007-7. Epub 2007 Apr 15. Mamm Genome. 2007. PMID: 17436120 - A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response.
Scheer N, Ross J, Rode A, Zevnik B, Niehaves S, Faust N, Wolf CR. Scheer N, et al. J Clin Invest. 2008 Sep;118(9):3228-39. doi: 10.1172/JCI35483. J Clin Invest. 2008. PMID: 18677425 Free PMC article. - Alternative splicing affects the function and tissue-specific expression of the human constitutive androstane receptor.
Arnold KA, Eichelbaum M, Burk O. Arnold KA, et al. Nucl Recept. 2004 Mar 25;2(1):1. doi: 10.1186/1478-1336-2-1. Nucl Recept. 2004. PMID: 15043764 Free PMC article. - Enteric Microbiota⁻Gut⁻Brain Axis from the Perspective of Nuclear Receptors.
Duszka K, Wahli W. Duszka K, et al. Int J Mol Sci. 2018 Jul 28;19(8):2210. doi: 10.3390/ijms19082210. Int J Mol Sci. 2018. PMID: 30060580 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases