Home LiteratureArticle Details
PMID: 21059794 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Xenobiotic metabolism, disposition, and regulation by receptors: from biochemical phenomenon to predictors of major toxicities.

Toxicological sciences : an official journal of the Society of Toxicology ·Vol. 120 Suppl 1 ·2011-03-00 ·Pages S49-75

Omiecinski CJ, Vanden Heuvel JP, Perdew GH, Peters JM

Abstract

To commemorate the 50th anniversary of the Society of Toxicology, this special edition article reviews the history and current scope of xenobiotic metabolism and transport, with special emphasis on the discoveries and impact of selected "xenobiotic receptors." This overall research realm has witnessed dynamic development in the past 50 years, and several of the key milestone events that mark the impressive progress in these areas of toxicological sciences are highlighted. From the initial observations regarding aspects of drug metabolism dating from the mid- to late 1800's, the area of biotransformation research witnessed seminal discoveries in the mid-1900's and onward that are remarkable in retrospect, including the discovery and characterization of the phase I monooxygenases, the cytochrome P450s. Further research uncovered many aspects of the biochemistry of xenobiotic metabolism, expanding to phase II conjugation and phase III xenobiotic transport. This led to hallmark developments involving integration of genomic technologies to elucidate the basis for interindividual differences in response to xenobiotic exposures and discovery of nuclear and soluble receptor families that selectively "sense" the chemical milieu of the mammalian cell and orchestrate compensatory changes in gene expression programming to accommodate complex xenobiotic exposures. This review will briefly summarize these developments and investigate the expanding roles of xenobiotic receptor biology in the underlying basis of toxicological response to chemical agents.

MeSH Terms
Animals Genomics Humans Inactivation, Metabolic Predictive Value of Tests Receptors, Cytoplasmic and Nuclear/physiology Xenobiotics/metabolism,pharmacokinetics,toxicity
Chemicals
Receptors, Cytoplasmic and Nuclear Xenobiotics
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Omiecinski Curtis J
Department of Veterinary and Biomedical Sciences, Center for Molecular Toxicology and Carcinogenesis, Penn State University, University Park, Pennsylvania 16802, USA. [email protected]
Vanden Heuvel John P
Perdew Gary H
Peters Jeffrey M
References (246)
246 references, click to expand
  1. The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptor.
    Biochemistry. 2010 Jan 19;49(2):393-400 PMID: 20000589
  2. A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response.
    J Clin Invest. 2008 Sep;118(9):3228-39 PMID: 18677425
  3. PPAR-beta/delta agonists for Type 2 diabetes and dyslipidemia: an adopted orphan still looking for a home.
    Expert Opin Investig Drugs. 2008 Oct;17(10):1465-71 PMID: 18808307
  4. Serum amyloid A: an acute-phase protein involved in tumour pathogenesis.
    Cell Mol Life Sci. 2009 Jan;66(1):9-26 PMID: 18726069
  5. Promoting effect of peroxisome proliferators in two-stage rat renal tumorigenesis.
    Cancer Lett. 1988 Dec 1;43(1-2):145-9 PMID: 3203323
  6. Cutting edge: TLR2 is a functional receptor for acute-phase serum amyloid A.
    J Immunol. 2008 Jul 1;181(1):22-6 PMID: 18566366
  7. Structure and function of sulfotransferases.
    Arch Biochem Biophys. 2001 Jun 15;390(2):149-57 PMID: 11396917
  8. ER alpha-AHR-ARNT protein-protein interactions mediate estradiol-dependent transrepression of dioxin-inducible gene transcription.
    J Biol Chem. 2005 Jun 3;280(22):21607-11 PMID: 15837795
  9. 2.1 A crystal structure of human PXR in complex with the St. John's wort compound hyperforin.
    Biochemistry. 2003 Feb 18;42(6):1430-8 PMID: 12578355
  10. Acute liver failure in the United States.
    Semin Liver Dis. 2003 Aug;23(3):217-26 PMID: 14523675
  11. Polarity and specific sequence requirements of peroxisome proliferator-activated receptor (PPAR)/retinoid X receptor heterodimer binding to DNA. A functional analysis of the malic enzyme gene PPAR response element.
    J Biol Chem. 1997 Aug 8;272(32):20108-17 PMID: 9242684
  12. Phenobarbital confers its diverse effects by activating the orphan nuclear receptor car.
    Drug Metab Rev. 2006;38(1-2):75-87 PMID: 16684649
  13. The coregulator exchange in transcriptional functions of nuclear receptors.
    Genes Dev. 2000 Jan 15;14(2):121-41 PMID: 10652267
  14. Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers.
    J Pharmacol Exp Ther. 2007 Jan;320(1):72-80 PMID: 17041008
  15. Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital.
    Mol Pharmacol. 2002 Jan;61(1):1-6 PMID: 11752199
  16. Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding.
    Endocrinology. 2001 Oct;142(10):4195-202 PMID: 11564675
  17. Arylamine N-acetyltransferases: structural and functional implications of polymorphisms.
    Toxicology. 2008 Dec 30;254(3):170-83 PMID: 18852012
  18. The mouse peroxisome proliferator activated receptor recognizes a response element in the 5' flanking sequence of the rat acyl CoA oxidase gene.
    EMBO J. 1992 Feb;11(2):433-9 PMID: 1537328
  19. Cancer incidence among patients using antiepileptic drugs: a long-term follow-up of 28,000 patients.
    Eur J Clin Pharmacol. 2002 May;58(2):137-41 PMID: 12012147
  20. Differential expression of peroxisome proliferator-activated receptor-alpha, -beta, and -gamma during rat embryonic development.
    Endocrinology. 1998 Jun;139(6):2748-54 PMID: 9607781
  21. PPAR alpha, more than PPAR delta, mediates the hepatic and skeletal muscle alterations induced by the PPAR agonist GW0742.
    Toxicol Sci. 2008 Oct;105(2):384-94 PMID: 18593727
  22. Crosstalk between peroxisome proliferator-activated receptor delta and VEGF stimulates cancer progression.
    Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19069-74 PMID: 17148604
  23. Mode of action in relevance of rodent liver tumors to human cancer risk.
    Toxicol Sci. 2006 Jan;89(1):51-6 PMID: 16221960
  24. Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay.
    Mol Endocrinol. 1997 Jun;11(6):779-91 PMID: 9171241
  25. Ligand activation of peroxisome proliferator-activated receptor beta inhibits colon carcinogenesis.
    Cancer Res. 2006 Apr 15;66(8):4394-401 PMID: 16618765
  26. The effect of connexin32 null mutation on hepatocarcinogenesis in different mouse strains.
    Carcinogenesis. 1999 Jul;20(7):1379-82 PMID: 10383916
  27. Studies on the induction of CO-binding pigments in liver microsomes by phenobarbital and 3-methylcholanthrene.
    Biochem Biophys Res Commun. 1967 Nov 30;29(4):521-6 PMID: 16496529
  28. Serum amyloid A binding to formyl peptide receptor-like 1 induces synovial hyperplasia and angiogenesis.
    J Immunol. 2006 Oct 15;177(8):5585-94 PMID: 17015746
  29. Activation of the aryl hydrocarbon receptor pathway enhances cancer cell invasion by upregulating the MMP expression and is associated with poor prognosis in upper urinary tract urothelial cancer.
    Carcinogenesis. 2010 Feb;31(2):287-95 PMID: 19755661
  30. Ligand selectivity and gene regulation by the human aryl hydrocarbon receptor in transgenic mice.
    Mol Pharmacol. 2009 Jun;75(6):1412-20 PMID: 19299563
  31. PPARbeta/delta ligands as modulators of the inflammatory response.
    Curr Opin Investig Drugs. 2008 May;9(5):463-9 PMID: 18465655
  32. Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease.
    Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18831-6 PMID: 19850873
  33. Cigarette smoke as a trigger for the dioxin receptor-mediated signaling pathway.
    Cancer Lett. 2007 Jul 18;252(2):184-94 PMID: 17189671
  34. Carcinogenesis by hepatic peroxisome proliferators: evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans.
    Crit Rev Toxicol. 1983;12(1):1-58 PMID: 6360536
  35. Effect of ligand activation of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) in human lung cancer cell lines.
    Toxicology. 2008 Dec 5;254(1-2):112-7 PMID: 18950674
  36. The cytochrome p450 homepage.
    Hum Genomics. 2009 Oct;4(1):59-65 PMID: 19951895
  37. Purification and characterization of liver microsomal cytochromes p-450: electrophoretic, spectral, catalytic, and immunochemical properties and inducibility of eight isozymes isolated from rats treated with phenobarbital or beta-naphthoflavone.
    Biochemistry. 1982 Nov 9;21(23):6019-30 PMID: 6758842
  38. Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor.
    Mol Endocrinol. 2005 Jun;19(6):1646-53 PMID: 15831521
  39. Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes.
    Mol Cell Biol. 2004 Sep;24(18):7931-40 PMID: 15340055
  40. The aryl hydrocarbon receptor complex.
    Annu Rev Pharmacol Toxicol. 1995;35:307-40 PMID: 7598497
  41. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma).
    J Biol Chem. 1995 Jun 2;270(22):12953-6 PMID: 7768881
  42. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors.
    Cell. 1992 Mar 6;68(5):879-87 PMID: 1312391
  43. Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification.
    Mol Pharmacol. 2002 Sep;62(3):638-46 PMID: 12181440
  44. The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization.
    Mol Cell. 2004 Dec 22;16(6):893-905 PMID: 15610733
  45. Nitrolinoleic acid: an endogenous peroxisome proliferator-activated receptor gamma ligand.
    Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2340-5 PMID: 15701701
  46. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions.
    J Clin Invest. 1998 Sep 1;102(5):1016-23 PMID: 9727070
  47. Differential susceptibility of mice humanized for peroxisome proliferator-activated receptor alpha to Wy-14,643-induced liver tumorigenesis.
    Carcinogenesis. 2006 May;27(5):1074-80 PMID: 16377806
  48. Ube2l3 gene expression is modulated by activation of the aryl hydrocarbon receptor: implications for p53 ubiquitination.
    Biochem Pharmacol. 2010 Sep 15;80(6):932-40 PMID: 20478272
  49. Nedd9/Hef1/Cas-L mediates the effects of environmental pollutants on cell migration and plasticity.
    Oncogene. 2009 Oct 15;28(41):3642-51 PMID: 19648964
  50. Hepatocellular carcinomas in acatalasemic mice treated with nafenopin, a hypolipidemic peroxisome proliferator.
    Cancer Res. 1976 Apr;36(4):1211-7 PMID: 177202
  51. SXR, a novel steroid and xenobiotic-sensing nuclear receptor.
    Genes Dev. 1998 Oct 15;12(20):3195-205 PMID: 9784494
  52. Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A protein.
    Lancet. 2001 Jul 7;358(9275):24-9 PMID: 11454373
  53. Pigments of rat liver microsomes.
    Arch Biochem Biophys. 1958 Jun;75(2):376-86 PMID: 13534720
  54. The structure of the nuclear hormone receptors.
    Steroids. 1999 May;64(5):310-9 PMID: 10406480
  55. Synthetic drugs and natural products as modulators of constitutive androstane receptor (CAR) and pregnane X receptor (PXR).
    Drug Metab Rev. 2006;38(1-2):51-73 PMID: 16684648
  56. Troglitazone and liver injury: in search of answers.
    Hepatology. 2005 Feb;41(2):237-46 PMID: 15657914
  57. Identification of a novel peroxisome proliferator-activated receptor (PPAR) gamma promoter in man and transactivation by the nuclear receptor RORalpha1.
    Biochem Biophys Res Commun. 2001 Sep 21;287(2):383-90 PMID: 11554739
  58. Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR.
    J Biol Chem. 1997 Sep 19;272(38):23565-71 PMID: 9295294
  59. Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells.
    Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9721-6 PMID: 18607004
  60. PPARbeta/delta agonist stimulates human lung carcinoma cell growth through inhibition of PTEN expression: the involvement of PI3K and NF-kappaB signals.
    Am J Physiol Lung Cell Mol Physiol. 2008 Jun;294(6):L1238-49 PMID: 18390835
  61. Coordinate regulation of human drug-metabolizing enzymes, and conjugate transporters by the Ah receptor, pregnane X receptor and constitutive androstane receptor.
    Biochem Pharmacol. 2009 Feb 15;77(4):689-99 PMID: 18606396
  62. Acute-phase proteins and other systemic responses to inflammation.
    N Engl J Med. 1999 Feb 11;340(6):448-54 PMID: 9971870
  63. Hepatic dysfunction associated with troglitazone.
    N Engl J Med. 1998 Mar 26;338(13):916-7 PMID: 9518284
  64. The xenobiotic compound 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene is an agonist ligand for the nuclear receptor CAR.
    Mol Cell Biol. 2000 May;20(9):2951-8 PMID: 10757780
  65. Antiapoptotic role of PPARbeta in keratinocytes via transcriptional control of the Akt1 signaling pathway.
    Mol Cell. 2002 Oct;10(4):721-33 PMID: 12419217
  66. Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha.
    Cancer Res. 2004 Jun 1;64(11):3849-54 PMID: 15172993
  67. Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals.
    Annu Rev Pharmacol Toxicol. 2003;43:309-34 PMID: 12540743
  68. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor.
    Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7500-2 PMID: 10852961
  69. Peroxisome proliferator-activated receptor alpha regulates a microRNA-mediated signaling cascade responsible for hepatocellular proliferation.
    Mol Cell Biol. 2007 Jun;27(12):4238-47 PMID: 17438130
  70. Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands.
    J Biol Chem. 2000 May 19;275(20):15122-7 PMID: 10748001
  71. Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated renal salt absorption.
    Nat Med. 2005 Aug;11(8):861-6 PMID: 16007095
  72. Characterization of a phenobarbital-responsive enhancer module in mouse P450 Cyp2b10 gene.
    J Biol Chem. 1997 Jun 6;272(23):14943-9 PMID: 9169466
  73. Evidence for a new P-450 hemoprotein in hepatic microsomes from methylcholanthrene treated rats.
    Biochem Biophys Res Commun. 1966 Sep 8;24(5):668-74 PMID: 5970499
  74. Liver-cell adenoma in an epileptic man on barbiturates.
    Histol Histopathol. 1989 Jul;4(3):301-3 PMID: 2562466
  75. Peroxisome proliferator-activated receptor gamma-dependent activity of indole ring-substituted 1,1-bis(3'-indolyl)-1-(p-biphenyl)methanes in cancer cells.
    Cancer Chemother Pharmacol. 2010 May;66(1):141-50 PMID: 19823826
  76. Mechanistic insights into the events that lead to synergistic induction of interleukin 6 transcription upon activation of the aryl hydrocarbon receptor and inflammatory signaling.
    J Biol Chem. 2010 Aug 6;285(32):24388-97 PMID: 20511231
  77. Diet, fatty acids, and regulation of genes important for heart disease.
    Curr Atheroscler Rep. 2004 Nov;6(6):432-40 PMID: 15485588
  78. 15-hydroxyeicosatetraenoic acid is a preferential peroxisome proliferator-activated receptor beta/delta agonist.
    Mol Pharmacol. 2010 Feb;77(2):171-84 PMID: 19903832
  79. Idiosyncratic liver injury: challenges and approaches.
    Toxicol Pathol. 2005;33(1):1-5 PMID: 15805049
  80. Characterization of the antiallergic drugs 3-[2-(2-phenylethyl) benzoimidazole-4-yl]-3-hydroxypropanoic acid and ethyl 3-hydroxy-3-[2-(2-phenylethyl)benzoimidazol-4-yl]propanoate as full aryl hydrocarbon receptor agonists.
    Chem Res Toxicol. 2008 Feb;21(2):472-82 PMID: 18179178
  81. The nuclear receptor superfamily: a personal retrospect on the first two decades.
    Mol Endocrinol. 2005 Jun;19(6):1418-28 PMID: 15914711
  82. Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: alternative promoter use and different splicing yield two mPPAR gamma isoforms.
    Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7921-5 PMID: 7644514
  83. Mechanistically-based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis.
    Hum Exp Toxicol. 1994 Nov;13 Suppl 2:S1-117 PMID: 7857698
  84. Drug uptake systems in liver and kidney: a historic perspective.
    Clin Pharmacol Ther. 2010 Jan;87(1):39-47 PMID: 19924123
  85. Alternatively spliced isoforms of the human constitutive androstane receptor.
    Nucleic Acids Res. 2003 Jun 15;31(12):3194-207 PMID: 12799447
  86. PPARbeta/delta selectively induces differentiation and inhibits cell proliferation.
    Cell Death Differ. 2006 Jan;13(1):53-60 PMID: 16021179
  87. Human constitutive androstane receptor mediates induction of CYP2B6 gene expression by phenytoin.
    J Biol Chem. 2004 Jul 9;279(28):29295-301 PMID: 15123723
  88. Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR.
    Science. 2002 Oct 11;298(5592):422-4 PMID: 12376703
  89. Rapid automated enzyme immunoassay of serum amyloid A.
    Clin Chem. 1994 Jul;40(7 Pt 1):1284-90 PMID: 8013100
  90. Meclizine is an agonist ligand for mouse constitutive androstane receptor (CAR) and an inverse agonist for human CAR.
    Mol Endocrinol. 2004 Oct;18(10):2402-8 PMID: 15272053
  91. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4318-23 PMID: 9113987
  92. The ontogeny of peroxisome-proliferator-activated receptor gene expression in the mouse and rat.
    Proc Biol Sci. 1992 Feb 22;247(1319):83-7 PMID: 1349185
  93. Localization of a phenobarbital-responsive element (PBRE) in the 5'-flanking region of the rat CYP2B2 gene.
    Gene. 1995 Jun 9;158(2):263-8 PMID: 7607552
  94. Phenobarbital response elements of cytochrome P450 genes and nuclear receptors.
    Annu Rev Pharmacol Toxicol. 2001;41:123-43 PMID: 11264453
  95. The metabolism of methylated aminoazo dyes. V. Evidence for induction of enzyme synthesis in the rat by 3-methylcholanthrene.
    Cancer Res. 1956 Jun;16(5):450-9 PMID: 13330038
  96. Genomic profiling in nuclear receptor-mediated toxicity.
    Toxicol Pathol. 2007 Jun;35(4):474-94 PMID: 17562482
  97. Dephosphorylation of threonine 38 is required for nuclear translocation and activation of human xenobiotic receptor CAR (NR1I3).
    J Biol Chem. 2009 Dec 11;284(50):34785-92 PMID: 19858220
  98. Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators.
    Mol Cell Biol. 1995 Jun;15(6):3012-22 PMID: 7539101
  99. The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity.
    J Biol Chem. 2004 Nov 19;279(47):49517-22 PMID: 15358766
  100. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat.
    Endocrinology. 1996 Jan;137(1):354-66 PMID: 8536636
  101. Biological potential of basophilic hepatocellular foci and hepatic adenoma induced by the peroxisome proliferator, Wy-14,643.
    Carcinogenesis. 1994 Jan;15(1):111-7 PMID: 7507413
  102. 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. 2006 May;7(4):349-65 PMID: 16724925
  103. PPAR-gamma activation fails to provide myocardial protection in ischemia and reperfusion in pigs.
    Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1314-23 PMID: 15528232
  104. Prostacyclin-mediated activation of peroxisome proliferator-activated receptor delta in colorectal cancer.
    Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13275-80 PMID: 11087869
  105. PPAR gamma and human metabolic disease.
    J Clin Invest. 2006 Mar;116(3):581-9 PMID: 16511590
  106. Phenobarbital responsiveness conferred by the 5'-flanking region of the rat CYP2B2 gene in transgenic mice.
    Gene. 1999 Mar 4;228(1-2):169-79 PMID: 10072770
  107. Transcriptional regulation of ABC drug transporters.
    Oncogene. 2003 Oct 20;22(47):7496-511 PMID: 14576854
  108. Evidence for ligand-mediated selective modulation of aryl hydrocarbon receptor activity.
    Mol Pharmacol. 2010 Feb;77(2):247-54 PMID: 19903824
  109. Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response.
    Mol Pharm. 2008 Jan-Feb;5(1):35-41 PMID: 18159929
  110. Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells.
    Nat Rev Immunol. 2010 May;10(5):365-76 PMID: 20414208
  111. A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements.
    Mol Cell Biol. 1994 Mar;14(3):1544-52 PMID: 8114692
  112. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors.
    Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7355-9 PMID: 8041794
  113. The organization, promoter analysis, and expression of the human PPARgamma gene.
    J Biol Chem. 1997 Jul 25;272(30):18779-89 PMID: 9228052
  114. Clofibrate causes an upregulation of PPAR-{alpha} target genes but does not alter expression of SREBP target genes in liver and adipose tissue of pigs.
    Am J Physiol Regul Integr Comp Physiol. 2007 Jul;293(1):R70-7 PMID: 17363680
  115. Genomic and non-genomic interactions of PPARalpha with xenobiotic-metabolizing enzymes.
    Trends Endocrinol Metab. 2004 Sep;15(7):324-30 PMID: 15350604
  116. Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor.
    Mol Pharmacol. 2005 Jun;67(6):1954-65 PMID: 15761118
  117. Gene expression profiling and differentiation assessment in primary human hepatocyte cultures, established hepatoma cell lines, and human liver tissues.
    Toxicol Appl Pharmacol. 2007 Jul 1;222(1):42-56 PMID: 17512962
  118. Cloning of a new member of the peroxisome proliferator-activated receptor gene family from mouse liver.
    J Biol Chem. 1993 Dec 25;268(36):26817-20 PMID: 8262913
  119. Structural insights into the promiscuity and function of the human pregnane X receptor.
    Curr Opin Drug Discov Devel. 2002 Jan;5(1):150-8 PMID: 11865669
  120. Retinoid X receptor-alpha-dependent transactivation by a naturally occurring structural variant of human constitutive androstane receptor (NR1I3).
    Mol Pharmacol. 2005 Nov;68(5):1239-53 PMID: 16099843
  121. [Pigmented hepatocellular adenoma of the liver caused by long-term use of phenobarbital].
    Rozhl Chir. 2003 Apr;82(4):192-5 PMID: 12795231
  122. Aryl hydrocarbon receptor (AhR) agonists suppress interleukin-6 expression by bone marrow stromal cells: an immunotoxicology study.
    Environ Health. 2003 Dec 16;2(1):16 PMID: 14678569
  123. Peroxisome proliferators and retinoids affect JEG-3 choriocarcinoma cell function.
    Endocrinology. 1994 Sep;135(3):1135-45 PMID: 8070357
  124. Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors.
    J Biol Chem. 1994 Nov 4;269(44):27337-43 PMID: 7961644
  125. Effects of aryl hydrocarbon receptor signaling on the modulation of TH1/TH2 balance.
    J Immunol. 2005 Dec 1;175(11):7348-56 PMID: 16301641
  126. PPARdelta regulates glucose metabolism and insulin sensitivity.
    Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3444-9 PMID: 16492734
  127. The nuclear receptor CAR is a regulator of thyroid hormone metabolism during caloric restriction.
    J Biol Chem. 2004 May 7;279(19):19832-8 PMID: 15004031
  128. Evolution of the ATP-binding cassette (ABC) transporter superfamily in vertebrates.
    Annu Rev Genomics Hum Genet. 2005;6:123-42 PMID: 16124856
  129. Regulation of peroxisome proliferator-activated receptor-beta/delta by the APC/beta-CATENIN pathway and nonsteroidal antiinflammatory drugs.
    Mol Carcinog. 2009 Oct;48(10):942-52 PMID: 19415698
  130. The orphan nuclear receptor constitutive active/androstane receptor is essential for liver tumor promotion by phenobarbital in mice.
    Cancer Res. 2004 Oct 15;64(20):7197-200 PMID: 15492232
  131. Role of PPAR alpha in the mechanism of action of the nongenotoxic carcinogen and peroxisome proliferator Wy-14,643.
    Carcinogenesis. 1997 Nov;18(11):2029-33 PMID: 9395198
  132. Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: implications for interindividual variability in response to drugs.
    J Clin Pharmacol. 2007 May;47(5):566-78 PMID: 17442683
  133. The RXR heterodimers and orphan receptors.
    Cell. 1995 Dec 15;83(6):841-50 PMID: 8521508
  134. CAR, driving into the future.
    Mol Endocrinol. 2004 Jul;18(7):1589-98 PMID: 14988430
  135. Characterization of the Ah receptor and aryl hydrocarbon hydroxylase induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin and benz(a)anthracene in the human A431 squamous cell carcinoma line.
    Cancer Res. 1988 May 1;48(9):2388-95 PMID: 2833345
  136. Nuclear receptor CAR represses TNFalpha-induced cell death by interacting with the anti-apoptotic GADD45B.
    PLoS One. 2010 Apr 12;5(4):e10121 PMID: 20404936
  137. Pregnane X receptor and constitutive androstane receptor at the crossroads of drug metabolism and energy metabolism.
    Drug Metab Dispos. 2010 Dec;38(12):2091-5 PMID: 20736325
  138. The toxicology of ligands for peroxisome proliferator-activated receptors (PPAR).
    Toxicol Sci. 2006 Apr;90(2):269-95 PMID: 16322072
  139. Di(2-ethylhexyl) phthalate is a highly potent agonist for the human constitutive androstane receptor splice variant CAR2.
    Mol Pharmacol. 2009 May;75(5):1005-13 PMID: 19211671
  140. Mechanisms of extrahepatic tumor induction by peroxisome proliferators in male CD rats.
    Toxicol Sci. 2001 Mar;60(1):44-55 PMID: 11222872
  141. Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARdelta agonist, on development of steatohepatitis in mice fed a methionine- and choline-deficient diet.
    Eur J Pharmacol. 2006 Apr 24;536(1-2):182-91 PMID: 16574099
  142. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces matrix metalloproteinase (MMP) expression and invasion in A2058 melanoma cells.
    Toxicol Appl Pharmacol. 2006 Feb 1;210(3):212-24 PMID: 15982688
  143. A novel role of the aryl hydrocarbon receptor (AhR) in centrosome amplification - implications for chemoprevention.
    Mol Cancer. 2010 Jun 17;9:153 PMID: 20565777
  144. Lack of phenobarbital-mediated promotion of hepatocarcinogenesis in connexin32-null mice.
    Cancer Res. 2000 Sep 15;60(18):5087-91 PMID: 11016633
  145. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor.
    Cell. 1994 Dec 30;79(7):1147-56 PMID: 8001151
  146. CYP1A induction and human risk assessment: an evolving tale of in vitro and in vivo studies.
    Drug Metab Dispos. 2007 Jul;35(7):1009-16 PMID: 17431034
  147. Ah receptor represses acute-phase response gene expression without binding to its cognate response element.
    Lab Invest. 2009 Jun;89(6):695-707 PMID: 19333233
  148. Fascin-1 promoter activity is regulated by CREB and the aryl hydrocarbon receptor in human carcinoma cells.
    PLoS One. 2009;4(4):e5130 PMID: 19340314
  149. Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells.
    J Exp Med. 2009 Jan 16;206(1):43-9 PMID: 19114668
  150. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4312-7 PMID: 9113986
  151. Use of the nuclear receptor PXR to predict drug interactions.
    Toxicology. 2000 Nov 16;153(1-3):1-10 PMID: 11090943
  152. Identification and characterization of 4-chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide (GSK3787), a selective and irreversible peroxisome proliferator-activated receptor delta (PPARdelta) antagonist.
    J Med Chem. 2010 Feb 25;53(4):1857-61 PMID: 20128594
  153. mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer.
    Genes Dev. 1994 May 15;8(10):1224-34 PMID: 7926726
  154. Resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity and abnormal liver development in mice carrying a mutation in the nuclear localization sequence of the aryl hydrocarbon receptor.
    J Biol Chem. 2003 May 16;278(20):17767-74 PMID: 12621046
  155. Myotoxicity associated with lipid-lowering drugs.
    Curr Opin Rheumatol. 2007 Jan;19(1):67-73 PMID: 17143099
  156. Decrease in the number of deaths from secondary amyloidosis in patients with juvenile rheumatoid arthritis.
    J Rheumatol. 1993 Jul;20(7):1201-3 PMID: 8371218
  157. Peroxisome proliferator-activated receptor delta as a molecular target to regulate lung cancer cell growth.
    FEBS Lett. 2005 Jul 4;579(17):3829-36 PMID: 15978581
  158. The dioxin receptor regulates the constitutive expression of the vav3 proto-oncogene and modulates cell shape and adhesion.
    Mol Biol Cell. 2009 Mar;20(6):1715-27 PMID: 19158396
  159. Identification of BCRP as transporter of benzo[a]pyrene conjugates metabolically formed in Caco-2 cells and its induction by Ah-receptor agonists.
    Carcinogenesis. 2005 Oct;26(10):1754-63 PMID: 15917307
  160. Quantitative expression patterns of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) protein in mice.
    Biochem Biophys Res Commun. 2008 Jul 4;371(3):456-61 PMID: 18442472
  161. PPARalpha agonist-induced rodent tumors: modes of action and human relevance.
    Crit Rev Toxicol. 2003;33(6):655-780 PMID: 14727734
  162. Ah receptor and NF-kappaB interactions, a potential mechanism for dioxin toxicity.
    J Biol Chem. 1999 Jan 1;274(1):510-5 PMID: 9867872
  163. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma.
    Cell. 1998 Apr 17;93(2):229-40 PMID: 9568715
  164. Expression and activity of aryl hydrocarbon receptors in development and cancer.
    Crit Rev Eukaryot Gene Expr. 2008;18(4):279-321 PMID: 18652561
  165. Development of a selective modulator of aryl hydrocarbon (Ah) receptor activity that exhibits anti-inflammatory properties.
    Chem Res Toxicol. 2010 May 17;23(5):955-66 PMID: 20423157
  166. Hepatic peroxisome proliferation: induction by two novel compounds structurally unrelated to clofibrate.
    Science. 1975 Nov 21;190(4216):787-9 PMID: 1198095
  167. Peroxisome proliferator-activated receptor alpha induces hepatic expression of the human bile acid glucuronidating UDP-glucuronosyltransferase 2B4 enzyme.
    J Biol Chem. 2003 Aug 29;278(35):32852-60 PMID: 12810707
  168. The glutathione S-transferases: an update.
    Hepatology. 1989 Mar;9(3):486-96 PMID: 2646197
  169. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators.
    Nature. 1990 Oct 18;347(6294):645-50 PMID: 2129546
  170. Peroxisome-proliferator-activated receptors and cancers: complex stories.
    Nat Rev Cancer. 2004 Jan;4(1):61-70 PMID: 14708026
  171. Breaking old paradigms: Th17 cells in autoimmune arthritis.
    Clin Immunol. 2009 Sep;132(3):295-304 PMID: 19403336
  172. Adverse health effects in humans exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
    Rev Environ Health. 2006 Apr-Jun;21(2):119-38 PMID: 16898675
  173. Carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in experimental models.
    Mol Nutr Food Res. 2006 Oct;50(10):897-907 PMID: 16977593
  174. Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor.
    J Biol Chem. 2002 Jan 25;277(4):2908-15 PMID: 11706036
  175. Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects.
    J Biol Chem. 1999 Mar 5;274(10):6718-25 PMID: 10037770
  176. Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling.
    Toxicol Sci. 2010 May;115(1):89-97 PMID: 20106948
  177. Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-1alpha.
    Cell. 2005 Aug 26;122(4):505-15 PMID: 16122419
  178. Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats.
    Diabetes. 1988 Nov;37(11):1549-58 PMID: 3053303
  179. PPARgamma3 mRNA: a distinct PPARgamma mRNA subtype transcribed from an independent promoter.
    FEBS Lett. 1998 Oct 30;438(1-2):55-60 PMID: 9821958
  180. Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction.
    Mol Cell Biol. 2005 Nov;25(22):10040-51 PMID: 16260617
  181. Immunochemical evidence for six forms of rat liver cytochrome P450 obtained using antibodies against purified rat liver cytochromes P450 and P448.
    Mol Pharmacol. 1976 Sep;12(5):746-58 PMID: 825720
  182. Role of peroxisome-proliferator-activated receptor beta/delta (PPARbeta/delta) in gastrointestinal tract function and disease.
    Clin Sci (Lond). 2008 Aug;115(4):107-27 PMID: 18616431
  183. Induction of phase I, II and III drug metabolism/transport by xenobiotics.
    Arch Pharm Res. 2005 Mar;28(3):249-68 PMID: 15832810
  184. Non-carcinogenic effects of TCDD in animals.
    Food Addit Contam. 2000 Apr;17(4):275-88 PMID: 10912242
  185. PXR and CAR in energy metabolism.
    Trends Endocrinol Metab. 2009 Aug;20(6):273-9 PMID: 19595610
  186. Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice.
    J Biol Chem. 2004 May 21;279(21):22250-7 PMID: 15004017
  187. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins.
    Nature. 2008 May 1;453(7191):106-9 PMID: 18362914
  188. Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers.
    Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2160-4 PMID: 8384714
  189. A new cytochrome in liver microsomes.
    J Biol Chem. 1962 Apr;237:1375-6 PMID: 14482007
  190. The selective aryl hydrocarbon receptor modulator 6-methyl-1,3,8-trichlorodibenzofuran inhibits prostate tumor metastasis in TRAMP mice.
    Biochem Pharmacol. 2009 Apr 1;77(7):1151-60 PMID: 19166822
  191. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants.
    Biochim Biophys Acta. 1976 Nov 11;455(1):152-62 PMID: 990323
  192. The aryl hydrocarbon receptor complex and the control of gene expression.
    Crit Rev Eukaryot Gene Expr. 2008;18(3):207-50 PMID: 18540824
  193. Interactions of indolo[3,2-b]carbazoles and related polycyclic aromatic hydrocarbons with specific binding sites for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver.
    Mol Pharmacol. 1993 Aug;44(2):336-45 PMID: 8394990
  194. Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. Homology to peroxisome proliferator-activated receptors.
    J Biol Chem. 1995 Feb 3;270(5):2367-71 PMID: 7836471
  195. PPAR-gamma regulates osteoclastogenesis in mice.
    Nat Med. 2007 Dec;13(12):1496-503 PMID: 18059282
  196. Nature of the hepatomegalic effect produced by ethyl-chlorophenoxy-isobutyrate in the rat.
    Nature. 1965 Nov 27;208(5013):856-8 PMID: 5870099
  197. T0901317 is a potent PXR ligand: implications for the biology ascribed to LXR.
    FEBS Lett. 2007 May 1;581(9):1721-6 PMID: 17418145
  198. Cellular and pharmacological selectivity of the peroxisome proliferator-activated receptor-beta/delta antagonist GSK3787.
    Mol Pharmacol. 2010 Sep;78(3):419-30 PMID: 20516370
  199. Structure and function of glutathione S-transferases.
    Biochim Biophys Acta. 1994 Mar 16;1205(1):1-18 PMID: 8142473
  200. Activation of mouse and human peroxisome proliferator-activated receptors (PPARs) by phthalate monoesters.
    Toxicol Sci. 2004 Nov;82(1):170-82 PMID: 15310864
  201. Serum amyloid A activates nuclear factor-kappaB in rheumatoid synovial fibroblasts through binding to receptor of advanced glycation end-products.
    J Rheumatol. 2008 May;35(5):752-6 PMID: 18322992
  202. The constitutive androstane receptor is an anti-obesity nuclear receptor that improves insulin sensitivity.
    J Biol Chem. 2009 Sep 18;284(38):25984-92 PMID: 19617349
  203. A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer.
    Mol Cell. 2004 Dec 22;16(6):919-28 PMID: 15610735
  204. Dietary flavonoids activate the constitutive androstane receptor (CAR).
    J Agric Food Chem. 2010 Feb 24;58(4):2168-73 PMID: 20099825
  205. Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxygenase.
    Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17073-8 PMID: 18952840
  206. Cyclooxygenase-2 promoter activation by the aromatic hydrocarbon receptor in breast cancer mcf-7 cells: repressive effects of conjugated linoleic acid.
    Nutr Cancer. 2007;59(2):248-57 PMID: 18001219
  207. Regulation of human hepatic hydroxysteroid sulfotransferase gene expression by the peroxisome proliferator-activated receptor alpha transcription factor.
    Mol Pharmacol. 2005 Apr;67(4):1257-67 PMID: 15635043
  208. Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon receptor.
    Exp Cell Res. 2006 Nov 1;312(18):3585-94 PMID: 16952353
  209. Coordinate transcriptional regulation of transport and metabolism.
    Methods Enzymol. 2005;400:511-30 PMID: 16399367
  210. Ligand activation of peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) attenuates carbon tetrachloride hepatotoxicity by downregulating proinflammatory gene expression.
    Toxicol Sci. 2008 Oct;105(2):418-28 PMID: 18622026
  211. Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)--synthesis and biological activity.
    Bioorg Med Chem Lett. 2003 May 5;13(9):1517-21 PMID: 12699745
  212. Three-dimensional quantitative structure-activity relationships of dioxins and dioxin-like compounds: model validation and Ah receptor characterization.
    Chem Res Toxicol. 1995 Sep;8(6):847-58 PMID: 7492734
  213. Sorting out the functional role(s) of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) in cell proliferation and cancer.
    Biochim Biophys Acta. 2009 Dec;1796(2):230-41 PMID: 19505534
  214. The roles of nuclear receptors CAR and PXR in hepatic energy metabolism.
    Drug Metab Pharmacokinet. 2008;23(1):8-13 PMID: 18305370
  215. Nuclear receptors constitutive androstane receptor and pregnane X receptor ameliorate cholestatic liver injury.
    Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):2063-8 PMID: 15684063
  216. Nuclear receptor coactivator SRC-1 interacts with the Q-rich subdomain of the AhR and modulates its transactivation potential.
    Gene Expr. 1999;8(5-6):273-86 PMID: 10947077
  217. Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands do not potentiate growth of human cancer cell lines.
    Carcinogenesis. 2007 Dec;28(12):2641-9 PMID: 17693664
  218. CAR and PXR: the xenobiotic-sensing receptors.
    Steroids. 2007 Mar;72(3):231-46 PMID: 17284330
  219. Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome.
    Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15924-9 PMID: 14676330
  220. 6-Methyl-1,3,8-trichlorodibenzofuran (MCDF) as an antiestrogen in human and rodent cancer cell lines: evidence for the role of the Ah receptor.
    Toxicol Appl Pharmacol. 1992 Apr;113(2):311-8 PMID: 1313996
  221. The role of peroxisome proliferator-activated receptor-beta/delta in epithelial cell growth and differentiation.
    Cell Signal. 2006 Jan;18(1):9-20 PMID: 16109478
  222. International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor.
    Pharmacol Rev. 2006 Dec;58(4):742-59 PMID: 17132852
  223. Ligand activation of peroxisome proliferator-activated receptor-beta/delta(PPARbeta/delta) inhibits cell growth of human N/TERT-1 keratinocytes.
    Cell Signal. 2007 Jun;19(6):1163-71 PMID: 17254750
  224. Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes.
    J Biol Chem. 2003 May 9;278(19):17277-83 PMID: 12611900
  225. Evidence that ligand binding is a key determinant of Ah receptor-mediated transcriptional activity.
    Arch Biochem Biophys. 2005 Oct 1;442(1):59-71 PMID: 16137638
  226. The aryl hydrocarbon receptor is required for developmental closure of the ductus venosus in the neonatal mouse.
    Mol Pharmacol. 2005 Mar;67(3):714-20 PMID: 15590894
  227. Substituted flavones as aryl hydrocarbon (Ah) receptor agonists and antagonists.
    Biochem Pharmacol. 1996 Apr 26;51(8):1077-87 PMID: 8866830
  228. Role of the constitutive androstane receptor in xenobiotic-induced thyroid hormone metabolism.
    Endocrinology. 2005 Mar;146(3):995-1002 PMID: 15564320
  229. [The acceleration of evipan oxidation and the demethylation of methylaminopyrine by barbiturates].
    Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1959;237:296-307 PMID: 14437294
  230. Use of 2-azido-3-[125I]iodo-7,8-dibromodibenzo-p-dioxin as a probe to determine the relative ligand affinity of human versus mouse aryl hydrocarbon receptor in cultured cells.
    Mol Pharmacol. 2004 Jul;66(1):129-36 PMID: 15213304
  231. PPARgamma and PPARdelta negatively regulate specific subsets of lipopolysaccharide and IFN-gamma target genes in macrophages.
    Proc Natl Acad Sci U S A. 2003 May 27;100(11):6712-7 PMID: 12740443
  232. 2-cyano-lup-1-en-3-oxo-20-oic acid, a cyano derivative of betulinic acid, activates peroxisome proliferator-activated receptor gamma in colon and pancreatic cancer cells.
    Carcinogenesis. 2007 Nov;28(11):2337-46 PMID: 17724373
  233. Abnormal liver development and resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in mice carrying a mutation in the DNA-binding domain of the aryl hydrocarbon receptor.
    Toxicol Sci. 2008 Nov;106(1):83-92 PMID: 18660548
  234. Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine nongenotoxic hepatocarcinogens phenobarbital and chlordane in vivo.
    Toxicol Sci. 2010 Aug;116(2):452-66 PMID: 20403969
  235. Peroxisome proliferator-activated receptor-beta/delta protects against chemically induced liver toxicity in mice.
    Hepatology. 2008 Jan;47(1):225-35 PMID: 18038451
  236. A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR.
    J Clin Invest. 2004 Jan;113(1):137-43 PMID: 14702117
  237. The aryl hydrocarbon receptor sans xenobiotics: endogenous function in genetic model systems.
    Mol Pharmacol. 2007 Sep;72(3):487-98 PMID: 17535977
  238. PPARalpha: mechanism of species differences and hepatocarcinogenesis of peroxisome proliferators.
    Toxicology. 2008 Apr 3;246(1):2-8 PMID: 18006136
  239. A functional cross-talk between liver X receptor-α and constitutive androstane receptor links lipogenesis and xenobiotic responses.
    Mol Pharmacol. 2010 Oct;78(4):666-74 PMID: 20592274
  240. DNA binding properties of peroxisome proliferator-activated receptor subtypes on various natural peroxisome proliferator response elements. Importance of the 5'-flanking region.
    J Biol Chem. 1997 Oct 3;272(40):25252-9 PMID: 9312141
  241. Enzyme inducers improve insulin sensitivity in non-insulin-dependent diabetic subjects.
    Diabetes. 1985 Sep;34(9):911-6 PMID: 3896900
  242. Loss of the aryl hydrocarbon receptor induces hypoxemia, endothelin-1, and systemic hypertension at modest altitude.
    Hypertension. 2008 Mar;51(3):803-9 PMID: 18212270
  243. Role of hemoprotein P-450 in fatty acid omega-hydroxylation in a soluble enzyme system from liver microsomes.
    J Biol Chem. 1968 Mar 25;243(6):1331-2 PMID: 4385007
  244. 2-Cyano-3,12-dioxoolean-1,9-dien-28-oic acid and related compounds inhibit growth of colon cancer cells through peroxisome proliferator-activated receptor gamma-dependent and -independent pathways.
    Mol Pharmacol. 2005 Jul;68(1):119-28 PMID: 15798084
  245. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway.
    Cell. 1998 Jan 9;92(1):73-82 PMID: 9489701
  246. Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR.
    Arch Biochem Biophys. 2005 Jan 15;433(2):387-96 PMID: 15581595
Article Info
Journal
Toxicological sciences : an official journal of the Society of Toxicology
Abbr.
Toxicol Sci
ISSN
1096-0929
DOI
10.1093/toxsci/kfq338
Email
[email protected]
Published
2011-03-00
Epub
2010-00-08
Pages
S49-75
Language
English
Region
United States
NLM ID
9805461
PMCID
PMC3145385
Subset
IM
Grants
NIGMS NIH HHS · R01 GM066411 · United States
NIGMS NIH HHS · GM066411 · United States
NCI NIH HHS · CA140369 · United States
NCI NIH HHS · R01 CA141029 · United States
NIEHS NIH HHS · ES04869 · United States
NIEHS NIH HHS · ES016358 · United States
NCI NIH HHS · CA141029 · United States
NCI NIH HHS · CA124533 · United States
External Links
PubMed source DOI: 10.1093/toxsci/kfq338 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2