Publication Cover
Xenobiotica
the fate of foreign compounds in biological systems
Volume 46, 2016 - Issue 3
286
Views
9
CrossRef citations to date
0
Altmetric
General Xenobiochemistry

Characterization of ligand-dependent activation of bovine and pig constitutive androstane (CAR) and pregnane X receptors (PXR) with interspecies comparisons

, , , , , , & show all
Pages 200-210 | Received 01 Jun 2015, Accepted 05 Jun 2015, Published online: 07 Jul 2015

References

  • Andersin T, Väisänen S, Carlberg C. (2003). The critical role of carboxyterminal amino acids in ligand-dependent and -independent transactivation of the constitutive androstane receptor. Mol Endocrinol 17:234–46
  • Cantiello M, Carletti M, Dacasto M, et al. (2008). Cytochrome P450 inhibition profile in liver of veal calves administered of 17β-estradiol, clenbuterol, and dexamethasone for growth-promoting purposes. Food Chem Toxicol 46:2849–55
  • Chrencik JE, Orans J, Moore LB, et al. (2005). Structural disorder in the complex of human pregnane X receptor and the macrolide antibiotic rifampicin. Mol Endocrinol 19:1125–34
  • di Masi A, De Marinis E, Ascenzi P, et al. (2009). Nuclear receptors CAR and PXR: molecular, functional, and biomedical aspects. Mol Aspects Med 30:297–343
  • Dong B, Lee JS, Park YY, et al. (2015). Activating CAR and β-catenin induces uncontrolled liver growth and tumorigenesis. Nat Commun 6:5944
  • Dou W, Mukherjee S, Li H, et al. (2012). Alleviation of gut inflammation by Cdx2/PXR pathway in a mouse model of chemical colitis. PLoS One 7:e36075
  • Elias A, High AA, Mishra A, et al. (2014). Identification and characterization of phosphorylation sites within the pregnane X receptor protein. Biochem Pharmacol 87:360–70
  • Giantin M, Lopparelli R, Zancanella V, et al. (2010). Effects of illicit dexamethasone upon hepatic drug metabolizing enzymes and related transcription factors mRNAs and their potential use as biomarkers in cattle. J Agric Food Chem 58:1342–9
  • Goodwin B, Hodgson E, Liddle C. (1999). The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Mol Pharmacol 56:1329–39
  • Goodwin B, Redinbo MR, Kliewer SA. (2002). Regulation of CYP3A gene transcription by the pregnane X receptor. Annu Rev Pharmacol Toxicol 42:1–23
  • Gray MA, Peacock JN, Squires EJ. (2009). Characterization of the porcine constitutive androstane receptor (CAR) and its splice variants. Xenobiotica 39:915–30
  • Gray MA, Pollock CB, Schook LB, et al. (2010). Characterization of porcine pregnane X receptor, farnesoid X receptor and their splice variants. Exp Biol Med 235:718–36
  • Honkakoski P, Jääskeläinen I, Kortelahti M, et al. (2001). A novel drug-regulated gene expression system based on the nuclear receptor constitutive androstane receptor (CAR). Pharm Res 18:146–50
  • Janowski BA, Willy PJ, Devi TR, et al. (1996). An oxysterol signalling pathway mediated by the nuclear receptor LXRα. Nature 383:728–31
  • Jiang M, Xie W. (2013). Role of the constitutive androstane receptor in obesity and type 2 diabetes: a case study of the endobiotic function of a xenobiotic receptor. Drug Metab Rev 45:156–63
  • Jyrkkärinne J, Mäkinen J, Gynther J, et al. (2003). Molecular determinants of steroid inhibition for the mouse constitutive androstane receptor. J Med Chem 46:4687–95
  • Jyrkkärinne J, Windshügel B, Mäkinen J, et al. (2005). Amino acids important for ligand specificity of the human constitutive androstane receptor. J Biol Chem 280:5960–71
  • Köhle C, Schwarz M, Bock KW. (2008). Promotion of hepatocarcinogenesis in humans and animal models. Arch Toxicol 82:623–31
  • Koutsounas I, Theocharis S, Patsouris E, et al. (2013). Pregnane X receptor (PXR) at the crossroads of human metabolism and disease. Curr Drug Metab 14:341–50
  • Küblbeck J, Jyrkkärinne J, Molnár F, et al. (2011a). New in vitro tools to study human constitutive androstane receptor (CAR) biology: discovery and comparison of human CAR inverse agonists. Mol Pharm 8:2424–33
  • Küblbeck J, Laitinen T, Jyrkkärinne J, et al. (2011b). Use of comprehensive screening methods to detect selective human CAR activators. Biochem Pharmacol 82:1994–2007
  • Küblbeck J, Jyrkkärinne J, Poso A, et al. (2008). Discovery of substituted sulfonamides and thiazolidin-4-one derivatives as agonists of human constitutive androstane receptor. Biochem Pharmacol 76:1288–97
  • Lau AJ, Yang G, Rajaraman G, et al. (2012). Species-dependent and receptor-selective action of bilobalide on the function of constitutive androstane receptor and pregnane X receptor. Drug Metab Dispos 40:178–86
  • Li L, Chen T, Stanton JD, et al. (2008). The peripheral benzodiazepine receptor ligand 1-(2-chlorophenyl-methylpropyl)-3-isoquinoline-carboxamide is a novel antagonist of human constitutive androstane receptor. Mol Pharmacol 74:443–53
  • Lynch C, Pan Y, Li L, et al. (2014). Activation of the constitutive androstane receptor inhibits gluconeogenesis without affecting lipogenesis or fatty acid synthesis in human hepatocytes. Toxicol Appl Pharmacol 279:33–42
  • Mäkinen J, Frank C, Jyrkkärinne J, et al. (2002). Modulation of mouse and human phenobarbital-responsive enhancer module by nuclear receptors. Mol Pharmacol 62:366–78
  • Mäkinen J, Reinisalo M, Niemi K, et al. (2003). Dual action of oestrogens on the mouse constitutive androstane receptor. Biochem J 376:465–72
  • Maté ML, Ballent M, Larsen K, et al. (2015). Gene expression and enzyme function of two cytochrome P450 3A isoenzymes in rat and cattle precision cut liver slices. Xenobiotica 28:1–8
  • Molnár F, Küblbeck J, Jyrkkärinne J, et al. (2013). An update on the constitutive androstane receptor (CAR). Drug Metabol Drug Interact 28:79–93
  • Moore LB, Maglich JM, McKee DD, et al. (2002). Pregnane X receptor (PXR), constitutive androstane receptor (CAR), and benzoate X receptor (BXR) define three pharmacologically distinct classes of nuclear receptors. Mol Endocrinol 16:977–86
  • Mutoh S, Sobhany M, Moore R, et al. (2013). Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling. Sci Signal 6:ra31
  • Östberg T, Bertilsson G, Jendeberg L, et al. (2002). Identification of residues in the PXR ligand binding domain critical for species specific and constitutive activation. Eur J Biochem 269:4896–904
  • Papadopoulos JS, Agarwala R. (2007). COBALT: constraint-based alignment tool for multiple protein sequences. Bioinformatics 23:1073–9
  • Pondugula SR, Brimer-Cline C, Wu J, et al. (2009). A phosphomimetic mutation at threonine-57 abolishes transactivation activity and alters nuclear localization pattern of human pregnane X receptor. Drug Metab Dispos 37:719–30
  • Poso A, Honkakoski P. (2006). Ligand recognition by drug-activated nuclear receptors PXR and CAR: structural, site-directed mutagenesis and molecular modeling studies. Mini Rev Med Chem 6:937–47
  • Potterton E, McNicholas S, Krissinel E, et al. (2002). The CCP4 molecular graphics project. Acta Cryst D 58:1955–7
  • Quan J, Tian J. (2009). Circular polymerase extension cloning of complex gene libraries and pathways. PLoS One 4:e6441
  • Repo S, Jyrkkärinne J, Pulkkinen JT, et al. (2008). Ligand specificity of constitutive androstane receptor as probed by induced-fit docking and mutagenesis. J Med Chem 51:7119–31
  • Reschly EJ, Krasowski MD. (2006). Evolution and function of the NR1I nuclear hormone receptor subfamily (VDR, PXR, and CAR) with respect to metabolism of xenobiotics and endogenous compounds. Curr Drug Metab 7:349–65
  • Schwede T, Kopp J, Guex N, et al. (2003). SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Res 31:3381–5
  • Shukla SJ, Sakamuru S, Huang R, et al. (2011). Identification of clinically used drugs that activate pregnane X receptors. Drug Metab Dispos 39:151–9
  • Stanley LA, Horsburgh BC, Ross J, et al. (2006). PXR and CAR: nuclear receptors which play a pivotal role in drug disposition and chemical toxicity. Drug Metab Rev 38:515–97
  • Suino K, Peng L, Reynolds R, et al. (2004). The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization. Mol Cell 16:893–905
  • Swales K, Kakizaki S, Yamamoto Y, et al. (2005). Novel CAR-mediated mechanism for synergistic activation of two distinct elements within the human cytochrome P450 2B6 gene in HepG2 cells. J Biol Chem 280:3458–66
  • Tirona RG, Leake BF, Podust LM, et al. (2004). Identification of amino acids in rat pregnane X receptor that determine species-specific activation. Mol Pharmacol 65:36–44
  • Venkatesh M, Mukherjee S, Wang H, et al. (2014). Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity 41:296–310
  • Vignati LA, Bogni A, Grossi P, et al. (2004). A human and mouse pregnane X receptor reporter gene assay in combination with cytotoxicity measurements as a tool to evaluate species-specific CYP3A induction. Toxicology 199:23–33
  • Watkins RE, Maglich JM, Moore LB, et al. (2003). A crystal structure of human PXR in complex with the St. John's wort compound hyperforin. Biochemistry 42:1430–8
  • Watkins RE, Wisely GB, Moore LB, et al. (2001). The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science 292:2329–33
  • Willson TM, Kliewer SA. (2002). PXR, CAR and drug metabolism. Nat Rev Drug Discov 1:259–66
  • Windshügel B, Jyrkkärinne J, Vanamo J, et al. (2007). Comparison of homology models and X-ray structures of the nuclear receptor CAR: assessing the structural basis of constitutive activity. J Mol Graph Model 25:644–57
  • Wu B, Li S, Dong D. (2013). 3D structures and ligand specificities of nuclear xenobiotic receptors CAR, PXR and VDR. Drug Discov Today 18:574–81
  • Xu RX, Lambert MH, Wisely BB, et al. (2004). A structural basis for constitutive activity in the human CAR/RXRα heterodimer. Mol Cell 16:919–28
  • Yang H, Wang H. (2014). Signaling control of the constitutive androstane receptor (CAR). Protein Cell 5:113–23

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.