The molecular basis for differential dioxin sensitivity in birds : role of the aryl hydrocarbon receptor
Author Posting. © National Academy of Sciences, 2006. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 103 (2006): 6252-6257, doi:10.1073/pnas.05...
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ftwhoas:oai:darchive.mblwhoilibrary.org:1912/887 2023-05-15T15:56:21+02:00 The molecular basis for differential dioxin sensitivity in birds : role of the aryl hydrocarbon receptor Karchner, Sibel I. Franks, Diana G. Kennedy, Sean W. Hahn, Mark E. 2006-04-10 1902668 bytes application/pdf https://hdl.handle.net/1912/887 en_US eng National Academy of Sciences https://doi.org/10.1073/pnas.0509950103 Proceedings of the National Academy of Sciences 103 (2006): 6252-6257 https://hdl.handle.net/1912/887 doi:10.1073/pnas.0509950103 Proceedings of the National Academy of Sciences 103 (2006): 6252-6257 doi:10.1073/pnas.0509950103 Basic helix–loop–helix-PAS Comparative toxicology Mechanisms Risk assessment Susceptibility Article 2006 ftwhoas https://doi.org/10.1073/pnas.0509950103 2022-05-28T22:57:01Z Author Posting. © National Academy of Sciences, 2006. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 103 (2006): 6252-6257, doi:10.1073/pnas.0509950103. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons (HAHs) are highly toxic to most vertebrate animals, but there are dramatic differences in sensitivity among species and strains. Aquatic birds including the common tern (Sterna hirundo) are highly exposed to HAHs in the environment, but are up to 250-fold less sensitive to these compounds than the typical avian model, the domestic chicken (Gallus gallus). The mechanism of HAH toxicity involves altered gene expression subsequent to activation of the aryl hydrocarbon receptor (AHR), a basic helix–loop–helix-PAS transcription factor. AHR polymorphisms underlie mouse strain differences in sensitivity to HAHs and polynuclear aromatic hydrocarbons, but the role of the AHR in species differences in HAH sensitivity is not well understood. Here, we show that although chicken and tern AHRs both exhibit specific binding of [3H]TCDD, the tern AHR has a lower binding affinity and exhibits a reduced ability to support TCDD-dependent transactivation as compared to AHRs from chicken or mouse. We further show through use of chimeric AHR proteins and site-directed mutagenesis that the difference between the chicken and tern AHRs resides in the ligand-binding domain and that two amino acids (Val-325 and Ala-381) are responsible for the reduced activity of the tern AHR. Other avian species with reduced sensitivity to HAHs also possess these residues. These studies provide a molecular understanding of species differences in sensitivity to dioxin-like compounds and suggest an approach to using the AHR as a marker of dioxin susceptibility in wildlife. This research was supported by the National Oceanographic and Atmospheric Administration ... Article in Journal/Newspaper Common tern Sterna hirundo Woods Hole Scientific Community: WHOAS (Woods Hole Open Access Server) Proceedings of the National Academy of Sciences 103 16 6252 6257 |
institution |
Open Polar |
collection |
Woods Hole Scientific Community: WHOAS (Woods Hole Open Access Server) |
op_collection_id |
ftwhoas |
language |
English |
topic |
Basic helix–loop–helix-PAS Comparative toxicology Mechanisms Risk assessment Susceptibility |
spellingShingle |
Basic helix–loop–helix-PAS Comparative toxicology Mechanisms Risk assessment Susceptibility Karchner, Sibel I. Franks, Diana G. Kennedy, Sean W. Hahn, Mark E. The molecular basis for differential dioxin sensitivity in birds : role of the aryl hydrocarbon receptor |
topic_facet |
Basic helix–loop–helix-PAS Comparative toxicology Mechanisms Risk assessment Susceptibility |
description |
Author Posting. © National Academy of Sciences, 2006. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 103 (2006): 6252-6257, doi:10.1073/pnas.0509950103. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons (HAHs) are highly toxic to most vertebrate animals, but there are dramatic differences in sensitivity among species and strains. Aquatic birds including the common tern (Sterna hirundo) are highly exposed to HAHs in the environment, but are up to 250-fold less sensitive to these compounds than the typical avian model, the domestic chicken (Gallus gallus). The mechanism of HAH toxicity involves altered gene expression subsequent to activation of the aryl hydrocarbon receptor (AHR), a basic helix–loop–helix-PAS transcription factor. AHR polymorphisms underlie mouse strain differences in sensitivity to HAHs and polynuclear aromatic hydrocarbons, but the role of the AHR in species differences in HAH sensitivity is not well understood. Here, we show that although chicken and tern AHRs both exhibit specific binding of [3H]TCDD, the tern AHR has a lower binding affinity and exhibits a reduced ability to support TCDD-dependent transactivation as compared to AHRs from chicken or mouse. We further show through use of chimeric AHR proteins and site-directed mutagenesis that the difference between the chicken and tern AHRs resides in the ligand-binding domain and that two amino acids (Val-325 and Ala-381) are responsible for the reduced activity of the tern AHR. Other avian species with reduced sensitivity to HAHs also possess these residues. These studies provide a molecular understanding of species differences in sensitivity to dioxin-like compounds and suggest an approach to using the AHR as a marker of dioxin susceptibility in wildlife. This research was supported by the National Oceanographic and Atmospheric Administration ... |
format |
Article in Journal/Newspaper |
author |
Karchner, Sibel I. Franks, Diana G. Kennedy, Sean W. Hahn, Mark E. |
author_facet |
Karchner, Sibel I. Franks, Diana G. Kennedy, Sean W. Hahn, Mark E. |
author_sort |
Karchner, Sibel I. |
title |
The molecular basis for differential dioxin sensitivity in birds : role of the aryl hydrocarbon receptor |
title_short |
The molecular basis for differential dioxin sensitivity in birds : role of the aryl hydrocarbon receptor |
title_full |
The molecular basis for differential dioxin sensitivity in birds : role of the aryl hydrocarbon receptor |
title_fullStr |
The molecular basis for differential dioxin sensitivity in birds : role of the aryl hydrocarbon receptor |
title_full_unstemmed |
The molecular basis for differential dioxin sensitivity in birds : role of the aryl hydrocarbon receptor |
title_sort |
molecular basis for differential dioxin sensitivity in birds : role of the aryl hydrocarbon receptor |
publisher |
National Academy of Sciences |
publishDate |
2006 |
url |
https://hdl.handle.net/1912/887 |
genre |
Common tern Sterna hirundo |
genre_facet |
Common tern Sterna hirundo |
op_source |
Proceedings of the National Academy of Sciences 103 (2006): 6252-6257 doi:10.1073/pnas.0509950103 |
op_relation |
https://doi.org/10.1073/pnas.0509950103 Proceedings of the National Academy of Sciences 103 (2006): 6252-6257 https://hdl.handle.net/1912/887 doi:10.1073/pnas.0509950103 |
op_doi |
https://doi.org/10.1073/pnas.0509950103 |
container_title |
Proceedings of the National Academy of Sciences |
container_volume |
103 |
container_issue |
16 |
container_start_page |
6252 |
op_container_end_page |
6257 |
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1766391799764484096 |