Skip to main content
Log in

Role of AHR, AHRR and ARNT in response to dioxin-like PCBs in Spaurus aurata

  • Short Research and Discussion Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

The aryl hydrocarbon receptor (AHR) mediates a variety of biological responses to ubiquitous dioxin and PCB dioxin-like. AHR together with ARNT, AHRR, represent a novel basic helix-loop-helix/PAS family of transcriptional regulators. Their interplay may affect the xenobiotic response. The aim of this study was to investigate, by histological, immunohistochemical investigations and western-blot analysis, the expression of AHR, ARNT and AHRR in liver of seabrem (Spaurus aurata) after exposure at different time to dioxin-like PCB126 in order to deep the knowledge about their specific role. The findings showed a significant increase of AHR and ARNT expression in juvenile fishes after 12 h than control group. The induction of AHR and ARNT is also significant at 24 and 72 hours compared to the control group. Furthemore, induction of AHRR expression has proved to increase both 12 h but this induction does not seem significant to 24 and 72 hours. The most important data of this work is that the induction of AHRR, when the action of the toxic persistence substances, as dioxin and PCB-126, it is not enough to reduce AHR signaling and thus its hyperactivation leads to toxic effects in seabrem (Spaurus aurata). All this confirms the importance of AHR ligands as new class of drugs that can be directed against severe disease such as cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig.1
Fig.2
Fig.3

Similar content being viewed by others

References

  • Baba T, Mimura J, Gradin K, Kuroiwa A, Watanabe T, Matsuda Y, Inazawa J, Sogawa K, Fujii-Kuriyama Y (2001) Structure and expression of the Ah receptor repressor gene. J Biol Chem 276(35):33101–33110

    Article  CAS  Google Scholar 

  • Beischlag TV, Luis Morales J, Hollingshead BD, Perdew GH (2008) The aryl hydrocarbon receptor complex and the control of gene expression. Crit Rev Eukaryot Gene Expr 18(3):207–250

    Article  CAS  Google Scholar 

  • Bock KW, Köhle C (2006) Ah receptor: dioxin-mediated toxic responses as hints to deregulated physiologic functions. Biochem Pharmacol 72(4):393–404

    Article  CAS  Google Scholar 

  • Bunger MK, Moran SM, Glover E, Thomae TL, Lahvis GP, Lin BC, Bradfield CA (2003) 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 278(20):17767–17774

    Article  CAS  Google Scholar 

  • Calò M, Bitto A, Lo Cascio P, Polito F, Lauriano ER, Minutoli L, Altavilla D, Squadrito F (2009) Cytochrome P450 (CYP1A) induction in sea bream (Sparus aurata) gills and liver following exposure to polychlorobiphenyls (PCBs). Vet Res Commun 33(Suppl 1):181–184

    Article  Google Scholar 

  • Calò M, Alberghina D, Bitto A, Lauriano ER, Lo Cascio P (2010) Estrogenic followed by anti-estrogenic effects of PCBs exposure in juvenile fish (Spaurus aurata). Food Chem Toxicol 48(8–9):2458–2463

    Article  Google Scholar 

  • Calò M, Casella S, Panzera M, Lo Cascio P, Alberghina D, Piccione G (2012) Activation of the Ahr signalling pathway by polychlorobiphenyls causes a marked induction of cytochrome P450 only after depletion of vitellogenin in Sparus aurata. Environ Toxicol Pharmacol 34(3):735–742. doi:10.1016/j.etap.2012.09.014

    Article  Google Scholar 

  • Céspedes MA, Galindo MI, Couso JP (2010) Dioxin toxicity invivo results from an increase in the dioxin-independent transcriptional activity of the aryl hydrocarbon receptor. PLoS One 8:5(11)

    Google Scholar 

  • Denison MS, Soshilov AA, He G, DeGroot DE, Zhao B (2011) Exactly the same but different: promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor. Toxicol Sci 124(1):1–22

    Article  CAS  Google Scholar 

  • Feng S, Cao Z, Wang X (2013) Role of aryl hydrocarbon receptor in cancer. Biochim Biophys Acta 1836(2):197–210

    CAS  Google Scholar 

  • Fujii-Kuriyama Y, Kawajiri K (2010) Molecular mechanisms of the physiological functions of the aryl hydrocarbon (dioxin) receptor, a multifunctional regulator that senses and responds to environmental stimuli. Proc Jpn Acad Ser B Phys Biol Sci 86(1):40–53

    Article  CAS  Google Scholar 

  • Gjernes MH, Schlenk D, Arukwe A (2012) Estrogen receptor-hijacking by dioxin-like 3,3′4,4′,5-pentachlorobiphenyl (PCB126) in salmon hepatocytes involves both receptor activation and receptor protein stability. Aquat Toxicol 124–125:197–208

    Article  Google Scholar 

  • Haarmann-Stemmann T, Abel J (2006) The arylhydrocarbon receptor repressor (AhRR): structure, expression, and function. Biol Chem 387(9):1195–1199

    Article  CAS  Google Scholar 

  • Hahn ME, Allan LL, Sherr DH (2009) Regulation of constitutive and inducible AHR signaling: complex interactions involving the AHR repressor. Biochem Pharmacol 77(4):485–497

    Article  CAS  Google Scholar 

  • Jönsson M, Brandt I, Brunstöm B (2002) A gill filament-based EROD assay for monitoring waterborne dioxin-like pollutants in fish. Environ Sci Technol 36:3340–3344

    Article  Google Scholar 

  • Jönsson M, Abrahamson A, Brunström B, Brandt I, Ingebrigtsen K, Jørgensen EH (2003) EROD activity in gill filaments of anadromous and marine fish as a biomarker of dioxin-like pollutants. Comp Biochem Physiol C Toxicol Pharmacol 136(3):235–243

    Article  Google Scholar 

  • Kanno Y, Takane Y, Takizawa Y, Inouye Y (2008) Suppressive effect of aryl hydrocarbon receptor repressor on transcriptional activity of estrogen receptor alpha by protein–protein interaction in stably and transiently expressing cell lines. Mol Cell Endocrinol 291(1–2):87–94

    Article  CAS  Google Scholar 

  • Karchner SI, Franks DG, Powell WH, Hahn ME (2002) Regulatory interactions among three members of the vertebrate aryl hydrocarbon receptor family: AHR repressor, AHR1, and AHR2. Biol Chem 277(9):6949–6959

    Article  CAS  Google Scholar 

  • Karchner SI, Jenny MJ, Tarrant AM, Evans BR, Kang HJ, Bae I, Sherr DH, Hahn ME (2009) 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 29(13):3465–3477

    Article  CAS  Google Scholar 

  • Lee JS, Kim EY, Nomaru K, Iwata H (2011) Molecular and functional characterization of Aryl hydrocarbon receptor repressor from the chicken (Gallus gallus): interspecies similarities and differences. Toxicol Sci 119(2):319–334

    Article  CAS  Google Scholar 

  • Mimura J, Fujii-Kuriyama Y (2003) Functional role of AhR in the expression of toxic effects by TCDD. Biochim Biophys Acta 1619(3):263–268

    Article  CAS  Google Scholar 

  • Mimura J, Ema M, Sogawa K, Fujii-Kuriyama Y (1999) Identification of a novel mechanism of regulation of Ah (dioxin) receptor function. Genes Dev 13(1):20–25

    Article  CAS  Google Scholar 

  • Mortensen AS, Arukwe A (2008a) Activation of estrogen receptor signaling by the dioxin-like aryl hydrocarbon receptor agonist, 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) in salmon invitro system. Toxicol Appl Pharmacol 227(2):313–324

    Article  CAS  Google Scholar 

  • Mortensen AS, Arukwe A (2008b) Estrogenic effect of dioxin-like aryl hydrocarbon receptor (AhR) agonist (PCB congener 126) in salmon hepatocytes. Mar Environ Res 66(1):119–120

    Article  CAS  Google Scholar 

  • Nebert DW, Dalton TP, Okey AB, Gonzalez FJ.Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J Biol Chem 2004 Jun 4;279(23):23847–50. Epub 2004 Mar 17

  • Ohtake F, Baba A, Takada I, Okada M, Iwasaki K, Miki H, Takahashi S, Kouzmenko A, Nohara K, Chiba T, Fujii-Kuriyama Y, Kato S (2007) Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. Nature 446(7135):562–566

    Article  CAS  Google Scholar 

  • Ohtake F, Baba A, Fujii-Kuriyama Y, Intrinsic KS (2008) AhR function underlies cross-talk of dioxins with sex hormone signalings. Biochem Biophys Res Commun 370(4):541–546

    Article  CAS  Google Scholar 

  • Ohtake F, Fujii-Kuriyama Y, Kato S (2009) AhR acts as an E3 ubiquitin ligase to modulate steroid receptor functions. Biochem Pharmacol 77(4):474–484

    Article  CAS  Google Scholar 

  • Ohtake F, Fujii-Kuriyama Y, Kawajiri K, Kato S (2011) Cross-talk of dioxin and estrogen receptor signals through the ubiquitin system. J Steroid Biochem Mol Biol 127(1–2):102–107

    Article  CAS  Google Scholar 

  • Oshima M, Mimura J, Sekine H, Okawa H, Fujii-Kuriyama Y (2009) UMO modification regulates the transcriptional repressor function of aryl hydrocarbon receptor repressor. J Biol Chem 284(17):11017–11026

    Article  CAS  Google Scholar 

  • Pollenz RS (2002) The mechanism of AH receptor protein down-regulation (degradation) and its impact on AH receptor-mediated gene regulation. Chem Biol Interact 141(1–2):41–61

    Article  CAS  Google Scholar 

  • Powell WH, Hahn ME (2000) The evolution of aryl hydrocarbon signaling proteins: diversity of ARNT isoforms among fish species. Mar Environ Res 50(1–5):39–44

    Article  CAS  Google Scholar 

  • Powell WH, Karchner SI, Bright R, Hahn ME (1999) Functional diversity of vertebrate ARNT proteins: identification of ARNT2 as the predominant form of ARNT in the marine teleost. Fundulus heteroclitus. Arch Biochem Biophys 361(1):156–163

    Article  CAS  Google Scholar 

  • Safe S, McDougal A (2002) Mechanism of action and development of selective aryl hydrocarbon receptor modulators for treatment of hormone-dependent cancers (Review). Int J Oncol 20(6):1123–1128

    CAS  Google Scholar 

  • Safe S, Lee SO, Jin UH (2013) Role of the aryl hydrocarbon receptor in carcino genesis and potential as a drug target. Toxicol Sci Sep 135(1):1–16. doi:10.1093/toxsci/kft128

  • Schmidt JV, Bradfield CA (1996) Ah receptor signaling pathways. Annu Rev Cell Dev Biol 12:55–89

    Article  CAS  Google Scholar 

  • Woods M, Kumar A, Barton M, Woods A, Kookana R (2009) Localisation of estrogen responsive genes in the liver and testis of Murray rainbow fish Melanotaenia fluviatilis exposed to 17beta-estradiol. Mol Cell Endocrinol 303(1–2):57–66

    Article  CAS  Google Scholar 

  • Zudaire E, Cuesta N, Murty V, Woodson K, Adams L, Gonzalez N, Martínez A, Narayan G, Kirsch I, Franklin W, Hirsch F, Birrer M, Cuttitta F (2008) The aryl hydrocarbon receptor repressor is a putative tumor suppressor gene in multiple human cancers. J Clin Invest 118(2):640–650

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Patrizia Licata.

Additional information

Responsible editor: Henner Hollert

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Calò, M., Licata, P., Bitto, A. et al. Role of AHR, AHRR and ARNT in response to dioxin-like PCBs in Spaurus aurata . Environ Sci Pollut Res 21, 14226–14231 (2014). https://doi.org/10.1007/s11356-014-3321-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-014-3321-x

Keywords

Navigation