Molecular evidence predicts aryl hydrocarbon receptor ligand insensitivity in the peregrine falcon (Falco peregrines)

Fujisawa, Nozomi; Ikenaka, Yoshinori; Kim, Eun Young; Lee, Jinseon; Iwata, Hisato; Ishizuka, Mayumi

doi:10.1007/s10344-011-0559-1

Cited by 3 publications

(2 citation statements)

References 39 publications

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“…Despite the evolutionary conservation of the AHR-mediated signaling pathway in birds, earlier in vitro and in vivo studies have reported large interspecies differences in sensitivity to exposure to 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) and other DLCs1213. Some previous studies have suggested that an in vitro assay system constructed using AHR expression vectors from chicken and other avian species may be a valuable tool for evaluating interspecies differences in responses to DLCs, and consequently for assessing risks for the species concerned1415161718.…”

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Ecological factors drive natural selection pressure of avian aryl hydrocarbon receptor 1 genotypes

Hwang

Park

Bak

et al. 2016

Sci Rep

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The aryl hydrocarbon receptor (AHR) mediates dioxin toxicities. Several studies have suggested that two amino acid residues corresponding to the 324th and 380th positions in the ligand binding domain (LBD) of the chicken AHR1 (Ile_Ser as high sensitivity, Ile_Ala as moderate sensitivity, and Val_Ala as low sensitivity), could be an important factor determining dioxin sensitivity in avian species. Here, we analyzed the association between ecological factors and AHR1 LBD genotypes of 113 avian species. Cluster analyses showed that 2 major clusters and sub-clusters of the cluster 3 were associated with specific AHR1 genotypes depending on the food, habitat, and migration of the animal. The majority of the species with Ile_Ala type were the Passeriformes, which are omnivorous or herbivorous feeders in the terrestrial environment. The species with Val_Ala type was primarily composed of raptors and waterbirds, which have been exposed to naturally occurring dioxins. An in vitro reporter gene assay revealed that the sensitivity to a natural dioxin, 1,3,7-tribromodibenzo-p-dioxin was in the order of Ile_Ser > Ile_Ala > Val_Ala. These results suggest that ecological factors related to the exposure of natural dioxins contribute to natural selection of the avian AHR1 genotype, which consequently leads to different sensitivity to man-made dioxins.

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Ecological factors drive natural selection pressure of avian aryl hydrocarbon receptor 1 genotypes

Hwang

Park

Bak

et al. 2016

Sci Rep

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“…To overcome ethical and experimental difficulties due to the requirement of large number of birds/eggs in toxicological studies, development of an in vitro assay system to evaluate the AHR-mediated signaling for individual DRC congeners is indispensable. We have established an in vitro assay system where the AHR expression plasmid of species of interest was introduced to a reporter gene transactivation assay that has proven to be an alternative approach to wildlife testing for toxicological studies. − Other groups have also demonstrated the alternative of the in vitro AHR assay. − …”

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confidence: 99%

Alternative In Vitro Approach for Assessing AHR-Mediated CYP1A Induction by Dioxins in Wild Cormorant (Phalacrocorax carbo) Population

Thuruthippallil

Kubota

Kim

et al. 2013

Environ. Sci. Technol.

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Our line of papers revealed that the common (great) cormorant (Phalacrocorax carbo) possesses two isoforms of the aryl hydrocarbon receptor (ccAHR1 and ccAHR2). This paper addresses in vitro tests of the ccAHR signaling pathways to solve two questions: (1) whether there are functional differences in the two ccAHR isoforms, and (2) whether a molecular perturbation, cytochrome P450 1A (ccCYP1A) induction, in the population-level can be predicted from the in vitro tests. The transactivation potencies mediated by ccAHR1 and ccAHR2 were measured in COS-7 cells treated with 15 selected dioxins and related compounds (DRCs), where ccAHR1 or ccAHR2 expression plasmid and ccCYP1A5 promoter/enhancer-linked luciferase reporter plasmid were transfected. For congeners that exhibited dose-dependent luciferase activities, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) relative potencies (REPs) and induction equivalency factors (IEFs) were estimated. ccAHR1-IEF profile was similar to WHO avian TCDD toxic equivalency factor (TEF) profile except for dioxin-like polychlorinated biphenyls that showed lower IEFs in ccAHR1-driven reporter assay. ccAHR2-IEF profile was different from WHO TEFs and ccAHR1-IEFs. Notably, 2,3,4,7,8-PeCDF was more potent than TCDD for ccAHR2-mediated response. Using ccAHR1- and ccAHR2-IEFs and hepatic DRC concentrations in the Lake Biwa cormorant population, total TCDD induction equivalents (IEQs) were calculated for each ccAHR-mediated response. Nonlinear regression analyses provided significant sigmoidal relationships of ccAHR1- and ccAHR2-derived IEQs with hepatic ccCYP1A5 mRNA levels, supporting the results of in vitro ccAHR-mediated TCDD dose-response curves. Collectively, our in vitro AHR reporter assay potentially could be an alternative to molecular epidemiology of the species of concern regarding CYP1A induction by AHR ligands.

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Molecular evaluation of a new highly sensitive aryl hydrocarbon receptor in ostriches

et al. 2013

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A 1,000-fold difference has been reported in dioxin sensitivity between avian species. This difference is because the 2 amino acids in the type 1 aryl hydrocarbon receptor (AhR1), at positions 325 and 381, correspond to Leu324 and Ser380 in chickens. The chicken had been reported to be the only avian species to possess a sensitive form of AhR1. This is the first study to reveal that the ostrich (Struthio camelus), a nonchicken species, also has a pair of amino acids (Ile-325 and Ser-381) that show high ligand affinity. However, the alignment of the AhR1 cDNA sequence showed that the AhR sequence in the ostrich was different than that of other avian species even though the critical amino acids were observed at positions 325 and 381. Ostrich AhR1 was also evaluated in a heterologous expression study. Ostrich AhR1 showed very high transcriptional activity of the cytochrome P450 1A5 (CYP1A5) gene in African Green Monkey Cercopithecus aethiops kidney cells (COS-7) treated with Sudan III. In primary cultures of ostrich kidney cells, CYP1A5 expression was induced by Sudan III at a lower (or almost identical) concentration to that observed in the chicken. The present study revealed a new AhR ligand sensitive avian species (i.e., the ostrich).

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Molecular evidence predicts aryl hydrocarbon receptor ligand insensitivity in the peregrine falcon (Falco peregrines)

Cited by 3 publications

References 39 publications

Ecological factors drive natural selection pressure of avian aryl hydrocarbon receptor 1 genotypes

Ecological factors drive natural selection pressure of avian aryl hydrocarbon receptor 1 genotypes

Alternative In Vitro Approach for Assessing AHR-Mediated CYP1A Induction by Dioxins in Wild Cormorant (Phalacrocorax carbo) Population

Molecular evaluation of a new highly sensitive aryl hydrocarbon receptor in ostriches

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