MOLECULAR AND FUNCTIONAL PROPERTIES OF THE ATLANTIC COD (GADUS MORHUA) ARYL HYDROCARBON RECEPTORS AHR1A AND AHR2A

The aryl hydrocarbon receptor (Ahr) is a ligand-activated transcription factor that mediates the toxicity of halogenated and polycyclic aromatic hydrocarbons in vertebrates. Atlantic cod (Gadus morhua) has recently emerged as a model organism in environmental toxicology studies, and increased knowle...

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Bibliographic Details
Published in:Environmental Science & Technology
Main Authors: Aranguren-Abadía, Libe, Lille-Langøy, Roger, Madsen, Alexander K., Karchner, Sibel I., Franks, Diana G., Yadetie, Fekadu, Hahn, Mark E., Goksøyr, Anders, Karlsen, Odd André
Format: Text
Language:English
Published: 2020
Subjects:
Article
atlantic cod
Gadus morhua
Online Access:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003535/
http://www.ncbi.nlm.nih.gov/pubmed/31852180
https://doi.org/10.1021/acs.est.9b05312
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Summary:The aryl hydrocarbon receptor (Ahr) is a ligand-activated transcription factor that mediates the toxicity of halogenated and polycyclic aromatic hydrocarbons in vertebrates. Atlantic cod (Gadus morhua) has recently emerged as a model organism in environmental toxicology studies, and increased knowledge of Ahr-mediated responses to xenobiotics is imperative. Genome mining and phylogenetic analyses revealed two Ahr-encoding genes in the Atlantic cod genome, gmahr1a and gmahr2a. In vitro binding assays showed that both gmAhr proteins bind to TCDD, but stronger binding to gmAhr1a was observed. Transactivation studies with a reporter gene assay revealed that gmAhr1a is one order of magnitude more sensitive to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) than gmAhr2a, but the maximal response of the receptors were similar. Other well-known Ahr agonists, such as β-naphthoflavone (BNF), 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) and 6-formylindolo[3,2-b]carbazole (FICZ), also activated the gmAhr proteins, but gmAhr1a was in general the more sensitive receptor and produced the highest efficacies. Induction of cyp1a in exposed precision-cut cod liver slices confirmed the activation of the Ahr signaling pathway ex vivo. In conclusion, the differences in transcriptional activation by gmAhrs with various agonists, the distinct binding properties with TCDD and BNF, and the distinct tissue-specific expression profiles, indicate different functional specializations of the Atlantic cod Ahrs.

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