Role of Aryl Hydrocarbon Receptor in Circadian Clock Disruption and Metabolic Dysfunction

Environmental Health Insights

Volumn 10, Issue , 2016, Pages

  Jaeger, Cassie ^a   Tischkau, Shelley A ^a  

^a SOUTHERN ILLINOIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

aryl hydrocarbon receptor; circadian rhythms; metabolic syndrome

Indexed keywords

EID: 85071539418     PISSN: None     EISSN: 11786302     Source Type: Journal    
DOI: 10.4137/EHI.S38343     Document Type: Review

References (114)

1. Hahn A., Poland E., Glover E., Stegeman J., Photoaffinity labeling of the Ah receptor: phylogenetic survey of diverse vertebrate and invertebrate species. Arch Biochem Biophys. 1994; 310: 218–28.
2. Hahn M., Aryl hydrocarbon receptors: diversity and evolution. Chem Biol Interact. 2002; 141: 131–60.
3. Gu Y., Hogenesch J., Bradfield C., The PAS superfamily: sensors of environmental and developmental signals. Annu Rev Pharmacol Toxicol. 2000; 40: 519–61.
4. McGuire J., Okamoto K., Whitelaw M., Tanaka H., Poellinger L., Definition of a dioxin receptor mutant that is a constitutive activator of transcription: delineation of overlapping repression and ligand binding functions within the PAS domain. J Biol Chem. 2001; 276: 41841–9.
5. Reisz-Porszasz S., Probst M., Fukunaga B., Hankinson O., Identification of functional domains of the aryl hydrocarbon receptor nuclear translocator protein (ARNT). Mol Cell Biol. 1994; 14: 6075–86.
6. Rappe C., Buser H., Bosshardt H-P. Dioxins, Dibenzofurans and Other Polyhalogenated Aromatics: Production, Use, Formation, and Destruction. The New York Academy of Sciences, New York; 1979.
7. Bohonowych J., Denison M., Persistent binding of ligands to the aryl hydrocarbon receptor. Toxicol Sci. 2007; 98: 99–109.
8. United States Environmental Protection Agency. Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin and Related Compounds. National Academy of Sciences Review Draft National Center for Environmental Assessment, Office of Research and Development, Washinton, DC; 2004.
9. United States Environmental Protection Agency. Persistent Organic Pollutants: A Global Issue, a Global Response. 2015. https://www.epa.gov/international-cooperation/persistent-organic-pollutants-global-issue-global-response.
10. World Health Organization. Polychlorinated Biphenyls: Human Health Aspects (Concise International Chemical Assessment Document; 55). Geneva: World Health Organization; 2003.
11. Denison M., Nagy S., Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu Rev Pharmacol Toxicol. 2003; 43: 309–34.
12. Bjeldanes L., Kim J., Grose K., Bartholomew J., Bradfield C., Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Proc Natl Acad Sci USA. 1991; 88: 9543–7.
13. Ciolino H., Daschner P., Yeh G., Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1 A1 transcription differentially. Biochem J. 1999; 340: 715–22.
14. Barouki R., Coumoul X., Fernandez-Salquero P., The aryl hydrocarbon receptor, more than a xenobiotic-interacting protein. FEBS Lett. 2007; 581: 3608–15.
15. Girer N., Murray I., Omiecinski C., Perdew G., Hepatic aryl hydrocarbon receptor attenuates fibroblast growth factor 21 expression. J Biol Chem. 2016; 291(29): 15378–87.
16. Baker N., Shoemaker R., English V.. Effects of adipocyte aryl hydrocarbon receptor deficiency on PCB-induced disruption of glucose homeostasis in lean and obese mice. Environ Health Perspect. 2015; 123: 944–50.
17. Dever D., Adham Z., Thompson B.. Aryl hydrocarbon receptor deletion in cerebellar granule neuron precursors impairs neurogenesis. Dev Neurobiol. 2016; 76: 533–50.
18. Fritsche E., Schafer C., Calles C.. Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation. Proc Natl Acad Sci USA. 2007; 104: 8851–6.
19. Rannug U., Rannug A., Sjoberg U., Li H., Westerholm R., Bergman J., Structure elucidation of two tryptophan-derived, high affinity, Ah receptor ligands. Chem Biol. 1995; 2: 841–5.
20. Rannug A., Rannug U., Rosenkranz H.. Certain photooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances. J Biol Chem. 1987; 262: 15422–7.
21. Bergander L., Wincent E., Rannug A., Foroozesh M., Alworth W., Rannug U., Metabolic fate of the Ah receptor ligand 6-formylindolo[3,2-b]carbazole. Chem Biol Interact. 2004; 149: 151–64.
22. Mukai M., Tischkau S., Effects of tryptophan photoproducts in the circadian timing system: searching for a physiological role for aryl hydrocarbon receptor. Toxicol Sci. 2007; 95: 172–81.
23. Ikuta T., Eguchi H., Tachibana T., Yonenda Y., Kawajiri K., Nuclear localization and export signals of the human aryl hydrocarbon receptor. J Biol Chem. 1998; 273: 2895–904.
24. Fukunaga B., Probst M., Reisz-Porszasz S., Hankinson O., Identification of functional domains of the aryl hydrocarbon receptor. J Biol Chem. 1995; 270: 29270–8.
25. Ikuta T., Kobayashi Y., Kawajiri K., Phosphorylation of nuclear localization signal inhibits the ligand-dependent nuclear import of aryl hydrocarbon receptor. Biochem Biophys Res Commun. 2004; 317: 545–50.
26. Bacsi S., Reisz-Porszasz S., Hankinson O., Orientation of the heterodimeric aryl hydrocarbon (dioxin) receptor complex on its asymmetric DNA recognition sequence. Mol Pharmacol. 1995; 47: 432–8.
27. Shanle E., Xu W., Endocrine disrupting chemicals targeting estrogen receptor signaling: identification and mechanisms of action. Chem Res Toxicol. 2011; 24: 6–19.
28. Swedenborg E., Pongratz I., AhR and ARNT modulate ER signaling. Toxicology. 2010; 268: 132–8.
29. Feng S., Cao Z., Wang X., Role of aryl hydrocarbon receptor in cancer. Biochim Biophy Acta. 2013; 1836: 197–210.
30. Cuninkova L., Brown S., Peripheral circadian oscillators: interesting mechanisms and powerful tools. Ann NY Acad Sci. 2008; 1129: 358–70.
31. Ralph M., Foster R., Davis F., Menaker M., Transplanted suprachiasmatic nucleus determines circadian period. Science. 1990; 247: 975–8.
32. Hardin P., Hall J., Rosbash M., Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature. 1990; 343: 536–40.
33. Jin X., Shearman L., Weaver D., Zylka M., de Vries G., Reppert S., A molecular mechanism regulating rhythmic output from the superchiasmatic circadian clock. Cell. 1999; 96: 57–68.
34. Lee C., Etchegaray J., Cagampang F., Loudon A., Reppert S., Posttranslational mechanisms regulate the mammalian circadian clock. Cell. 2001; 107: 855–67.
35. McIntosh B., Hogenesch J., Bradfield C., Mammalian Per-Arnt-Sim proteins in environmental adaptation. Annu Rev Physiol. 2010; 72: 625–45.
36. Denison M., Soshilov A., He G., DeGroot D., Zhao B., Exactly the same but different: promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor. Toxicol Sci. 2011; 124: 1–22.
37. Yu W., Ikeda M., Abe H.. Characterization of three splice variants and genomic organization of the mouse Bmal1 gene. Biochem Biophys Res Commun. 1999; 260: 760–7.
38. Tischkau S., Jaeger C., Krager S., Circadian clock disruption in the mouse ovary in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Lett. 2011; 201: 116–22.
39. Xu C., Wang C., Krager S., Bottum K., Tischkau S., Aryl hydrocarbon receptor activation attenuates Per1 gene induction and influences circadian clock resetting. Toxicol Sci. 2013; 132: 368–78.
40. Xu C., Krager S., Liao D., Tischkau S., Disruption of CLOCK-BMAL1 transcriptional activity is responsible for aryl hydrocarbon receptor-mediated regulation of Period1 gene. Toxicol Sci. 2010; 115: 98–108.
41. Mukai M., Lin T., Peterson R., Cooke P., Tischkau S., Behavioral rhythmicity of mice lacking AhR and attenuation of light-induced phase shift by 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Biol Rhythms. 2008; 23: 200–10.
42. Petersen S., Curran M., Marconi S., Carpenter C., Lubbers L., McAbee M., Distribution of mRNAs encoding the arylhydrocarbon receptor, arylhydrocarbon receptor nuclear translocator, and arylhydrocarbon receptor nuclear translocator-2 in the rat brain and brainstem. J Comp Neurol. 2000; 427: 428–39.
43. Weber L., Ernst S., Stahl B., Rozman K., Tissue distribution and toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats after intravenous injection. Fundam Appl Toxicol. 1993; 21: 523–34.
44. Huang P., Rannug A., Ahlbom E., Hakansson H., Ceccatelli S., Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the expression of cytochrome P4501A1, the aryl hydrocarbon receptor, and the aryl hydrocarbon receptor nuclear translocator in rat brain and pituitary. Toxicol Appl Pharmacol. 2000; 169: 159–67.
45. Jones M., Weisenburger W., Sipes I., Russell D., Circadian alterations in prolactin, corticosterone, and thyroid hormone levels and down-regulation of prolactin receptor activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol. 1987; 87: 337–50.
46. Seefeld M., Corbett S., Keesey R., Peterson R., Characterization of the wasting syndrome in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol. 1984; 73: 311–22.
47. Yellon S., Singh D., Garrett T., Fagoaga O., Nehlsen-Cannarella S., Reproductive, neuroendocrine, and immune consequences of acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in the Siberian hamster. Biol Reprod. 2000; 63: 538–43.
48. Pohjanvirta R., Tuomisto J., 2,3,7,8-tetrachlorodibenzo-p-dioxin enhances responsiveness to post-ingestive satiety signals. Toxicology. 1990; 63: 285–99.
49. Pohjanvirta R., Tuomisto J., Linden J., Laitinen J., TCDD reduces serum melatonin levels in Long-Evans rats. Pharmacol Toxicol. 1989; 65: 239–40.
50. Linden J., Pohjanvirta R., Rahko T., Tuomisto J., TCDD decreases rapidly and persistently serum melatonin concentration without morphologically affecting the pineal gland in TCDD-resistant Han/Wistar rats. Pharmacol Toxicol. 1991; 69: 427–32.
51. Miller J., Settachan D., Frame L., Dickerson R., 2,3,7,8-Tetrachlorodibenzo-p-dioxin phase advances the deer mouse (Peromyscus manuculatur) circadian rhythm by altering expression of clock proteins. Organohalogen Compd. 1999; 42: 23–8.
52. Postuma R., Montplaisir J., Pelletier A.. Environmental risk factors for REM sleep behavior disorder: a multicenter case-control study. Neurology. 2012; 79: 428–34.
53. Qu X., Metz R., Porter W., Neuendorff N., Earnest B., Earnest D., The clock genes period 1 and period 2 mediate diurnal rhythms in dioxin-induced Cyp1 A1 expression in the mouse mammary gland and liver. Toxicol Lett. 2010; 196: 28–32.
54. Qu X., Metz R., Porter W., Cassone V., Earnest D., Disruption of clock gene expression alters responses of the aryl hydrocarbon receptor signaling pathway in the mouse mammary gland. Mol Pharmacol. 2007; 72: 1349–58.
55. Qu X., Metz R., Porter W., Cassone V., Earnest D., Disruption of period gene expression alters the inductive effects of dioxin on the AhR signaling pathway in the mouse liver. Toxicol Appl Pharmacol. 2009; 234: 370–7.
56. Garrison P., Denison M., Analysis of the murine AhR gene promoter. J Biochem Mol Toxicol. 2000; 14: 1–10.
57. Huang P., Ceccatelli S., Rannug A., A study on diurnal mRNA expression of CYP1A1, AHR, ARNT, and PER2 in rat pituitary and liver. Environ Toxicol Pharmacol. 2002; 11: 119–26.
58. Richardson V., Santostefano M., Birnbaum L., Daily cycle of bHLH-PAS proteins, Ah receptor and Arnt, in multiple tissues of female Sprague-Dawley rats. Biochem Biophys Res Commun. 1998; 252: 225–31.
59. Zhang J., Yeager R., Klaassen C., Circadian expression profiles of drug-processing genes and transcription factors in mouse liver. Drug Metab Dispos. 2009; 37: 106–15.
60. Ko H., Okino S., Ma Q, Whitlock J.J., Dioxin-induced CYP1 A1 transcription in vivo: the aromatic hydrocarbon receptor mediates transactivation, enhancer-promoter communication, and changes in chromatin structure. Mol Cell Biol. 1996; 16: 430–6.
61. Tanimura N., Kusunose N., Matsunaga N., Koyanagi S., Ohdo S., Aryl hydrocarbon receptor-mediated Cyp1a1 expression is modulated in a CLOCK-dependent circadian manner. Toxicology. 2011; 290: 203–7.
62. Sato S., Shirakawa H., Tomita S.. Low-dose dioxins alter gene expression related to cholesterol biosynthesis, lipogenesis, and glucose metabolism through the aryl hydrocarbon receptor-mediated pathway in mouse liver. Toxicol Appl Pharmacol. 2008; 229(1): 10–9.
63. Wang C., Xu C., Krager S., Bottum K., Liao D., Tischkau S., Aryl hydrocarbon receptor deficiency enhances insulin sensitivity and reduces PPAR-alpha pathway activity in mice. Environ Health Perspect. 2011; 119: 1739–44.
64. Danaei G., Finucane M., Lu Y.. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2-7 million participants. Lancet. 2011; 378: 31–40.
65. Karlsson B., Knutsson A., Lindahl B., Is there an association between shift work and having a metabolic syndrome? Results from a population based study of 27 485 people. Occup Environ Med. 2001; 58: 747–52.
66. Karlsson B., Knutsson A., Lindahl B., Alfredsson L., Metabolic disturbances in male workers with rotating three-shift work. Results of the WOLF study. Int Arch Occup Environ Health. 2003; 76: 424–30.
67. Pietroiusti A., Neri A., Somma G.. Incidence of metabolic syndrome among night-shift healthcare workers. Occup Environ Med. 2009; 67: 54–7.
68. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation. 2002; 106: 3143–421.
69. Barclay J., Husse J., Bode B.. Circadian desynchrony promotes metabolic disruption in a mouse model of shiftwork. PLoS One. 2012; 7: e37150.
70. Turek F., Joshu C., Kohsaka A.. Obesity and metabolic syndrome in circadian Clock mutant mice. Science. 2005; 308: 1043–5.
71. Mimura J., Fujii-Kuriyama Y., Functional role of AhR in the expression of toxic effects by TCDD. Biochim Biophys Acta. 2003; 1619: 263–8.
72. Calvert G., Sweeney M., Deddens J., Wall D., Evaluation of diabetes mellitus, serum glucose, and thyroid function among United States workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Occup Environ Med. 1999; 56: 270–6.
73. Cranmer M., Louie S., Kennedy R., Kern P., Fonseca V., Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with hyperinsulinemia and insulin resistance. Toxicol Sci. 2000; 56: 431–6.
74. Henriksen G., Ketchum N., Michalek J., Swaby J., Serum dioxin and diabetes mellitus in veterans of Operation Ranch Hand. Epidemiology. 1997; 8: 252–8.
75. Bertazzi P., Consonni D., Bachetti S.. Health effects of dioxin exposure: a 20-year mortality study. Am J Epidemiol. 2001; 153: 1031–44.
76. Warner M., Mocarelli P., Brambilla P.. Diabetes, metabolic syndrome, and obesity in relation to serum dioxin concentrations: the Seveso women's health study. Environ Health Perspect. 2013; 121: 906–11.
77. Arsenescu V., Arsenescu R., King V., Swanson H., Cassis L., Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis. Environ Health Perspect. 2008; 116: 761–8.
78. Kim M., Pelloux V., Guyot E.. Inflammatory pathway genes belong to major targets of persistent organic pollutants in adipose cells. Environ Health Perspect. 2012; 120: 508–14.
79. Baker N., Karounos M., English V.. Coplanar polychlorinated biphenyls impair glucose homeostasis in lean C57BL/6 mice and mitigate beneficial effects of weight loss on glucose homeostasis in obese mice. Environ Health Perspect. 2013; 121: 105–10.
80. Fujiyoshi P., Michalek J., Matsumura F., Molecular epidemiologic evidence for diabetogenic effects of dioxin exposure in U.S. Air force veterans of the Vietnam war. Environ Health Perspect. 2006; 114: 1677–83.
81. Ruan H., Hacohen N., Golub T., Van Parijs L., Lodish H., Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory. Diabetes. 2002; 51: 1319–36.
82. Dere E., Lo R., Celius T., Matthews J., Zacharewski T., Integration of genome-wide computation DRE search, AhR ChIP-chip and gene expression analyses of TCDD-elicited responses in the mouse liver. BMC Genomics. 2011; 12: 365.
83. Remillard R., Bunce N., Linking dioxins to diabetes: epidemiology and biologic plausibility. Environ Health Perspect. 2002; 110: 853–8.
84. Boverhof D., Burgoon L., Tashiro C.. Comparative toxicogenomic analysis of the hepatotoxic effects of TCDD in Sprague Dawley rats and C57BL/6 mice. Toxicol Sci. 2006; 94: 398–416.
85. Denison M.S., Heath-Pagliuso S., The Ah receptor: a regulator of the biochemical and toxicological actions of structurally diverse chemicals. Bull Environ Contam Toxicol. 1998; 61: 557–68.
86. Gasiewicz T., Kende A., Rucci G., Whitney B., Willey J., Analysis of structural requirements for Ah receptor antagonist activity: ellipticines, flavones, and related compounds. Biochem Pharmacol. 1996; 52: 1787–803.
87. Chiaro C., Patel R., Perdew G., 12(R)-Hydroxy-5(Z),8(Z),10(E),12(Z)-eicosatetraenoic acid [12(R)-HETE], an arachidonic acid derivative, is an activator of the aryl hydrocarbon receptor. Mol Pharmacol. 2008; 74: 1649–56.
88. Schaldach C., Riby J., Bjeldanes L., Lipoxin A4: a new class of ligand for the Ah receptor. Biochemistry. 1999; 38: 7594–600.
89. Seidel S., Winters G., Rogers W.. Activation of the Ah receptor signaling pathway by prostaglandins. J Biochem Mol Toxicol. 2001; 15: 187–96.
90. McMillan B., Bradfield C., The aryl hydrocarbon receptor is activated by modified low-density lipoprotein. Proc Natl Acad Sci USA. 2007; 104: 1412–7.
91. Moyer B., Rojas I., Kerley-Hamilton J.. Inhibition of the aryl hydrocarbon receptor prevents Western diet-induced obesity. Model for AHR activation by kynurenine via oxidized-LDL, TLR2/4, TGFβ, and IDO1. Toxicol Appl Pharmacol. 2016; 300: 13–24.
92. Jeuken A., Keser B., Khan E., Brouwer A., Koeman J., Denison M., Activation of the Ah receptor by extracts of dietary herbal supplements, vegetables, and fruits. J Agric Food Chem. 2003; 51: 5478–87.
93. Zhang S., Qin C., Safe S., Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context. Environ Health Perspect. 2003; 111: 1877–82.
94. Tittlemier S., Dietary exposure to a group of naturally produced organohalogens (halogenated dimethyl bipyrroles) via consumption of fish and seafood. J Agric Food Chem. 2004; 52: 2010–5.
95. Biljes D., Hammerschmidt-Kamper C., Kadow S.. Impaired glucose and lipid metabolism in ageing aryl hydrocarbon receptor deficient mice. EXCLI J. 2015; 14: 1153–63.
96. Phillips T., Hen R., Crabbe J., Complications associated with genetic background effects in research using knockout mice. Psychopharmacology. 1999; 147: 5–7.
97. Thackaberry E., Bedrick E., Goens M.. Insulin regulation in AhR-null mice: embryonic cardiac enlargement, neonatal macrosomia, and altered insulin regulation and response in pregnant and aging AhR-null females. Toxicol Sci. 2003; 76: 407–17.
98. Kerley-Hamilton J., Trask H., Ridley C.. Obesity is mediated by differential aryl hydrocarbon receptor signaling in mice fed a Western diet. Environ Health Perspect. 2012; 120: 1252–9.
99. Xu C., Wang C., Zhang Z.. Aryl hydrocarbon receptor deficiency protects mice from diet-induced adiposity and metabolic disorders through increased energy expenditure. Int J Obes (Lond). 2015; 39: 1300–9.
100. Eckel-Mahan K., Patel V., Mohney R., Vignola K., Baldi P., Sassone-Corsi P., Coordination of the transcriptome and metabolome by the circadian clock. Proc Natl Acad Sci USA. 2012; 109: 5541–6.
101. Eckel-Mahan K., Patel V., Mateo S.. Reprogramming of the circadian clock by nutritional challenge. Cell. 2013; 155: 1464–78.
102. Hatanaka F., Matsubara C., Myung J.. Genome-wide profiling of the core clock protein BMAL1 targets reveals a strict relationship with metabolism. Mol Cell Biol. 2010; 30: 5636–48.
103. Rey G., Cesbron F., Rougemont J., Reinke H., Brunner M., Naef F., Genome-wide and phase-specific DNA-binding rhythms of BMAL1 control circadian output functions in mouse liver. PLoS Biol. 2011; 9: e1000595.
104. Carlstedt-Duke J., Tissue distribution of the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat. Cancer Res. 1979; 39: 3172–6.
105. Carver L., Hogenesch J., Bradfield C., Tissue specific expression of the rat Ah-receptor and ARNT mRNAs. Nucleic Acids Res. 1994; 22: 3038–44.
106. FitzGerald C., Fernandez-Salguero P., Gonzalez F., Nebert D., Puga A., Differential regulation of mouse Ah receptor gene expression in cell lines of different tissue origins. Arch Biochem Biophys. 1996; 333: 170–8.
107. Balsalobre A., Damiola F., Schibler U., A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell. 1998; 93: 929–37.
108. Karchner S., Jenny M., Tarrant A.. The active form of human aryl hydrocarbon receptor (AHR) repressor lacks exon 8, and its Pro 185 and Ala 185 variants repress both AHR and hypoxia-inducible factor. Mol Cell Biol. 2009; 29: 3465–77.
109. Beedanagari S., Bebenek I., Bui P., Hankinson O., Resveratrol inhibits dioxin-induced expression of human CYP1A1 and CYP1B1 by inhibiting recruitment of the aryl hydrocarbon receptor complex and RNA polymerase II to the regulatory regions of the corresponding genes. Toxicol Sci. 2009; 110: 61–7.
110. Ciolino H., Daschner P., Wang T., Yeh G., Effect of curcumin on the aryl hydrocarbon receptor and cytochrome P450 1 A1 in MCF-7 human breast carcinoma cells. Biochem Pharmacol. 1998; 56: 197–206.
111. Kim S., Henry E., Kim D.. Novel compound 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-0-tolylazo-phenyl)-amide (CH-223191) prevents 2,3,7,8-TCDD-induced toxicity by antagonizing the aryl hydrocarbon receptor. Mol Pharmacol. 2006; 69: 1871–8.
112. Murray I., Flaveny C., DiNatale B.. Antagonism of aryl hydrocarbon receptor signaling by 6,2'4‘-trimethoxyflavone. J Pharmacol Exp Ther. 2010; 332: 135–44.
113. Smith K., Murray I., Tanos R.. Identification of a high-affinity ligand that exhitibs, complete aryl hydrocarbon receptor antagonism. J Pharmacol Exp Ther. 2011; 338: 318–27.
114. Zhao B., Degroot D., Hayashi A., He G., Denison M., CH223191 is a ligand-selective. Antagonist of the Ah (Dioxin) receptor. Toxicol Sci. 2010; 117: 393–403.