Differences in activation of aryl hydrocarbon receptors of white sturgeon relative to lake sturgeon are predicted by identities of key amino acids in the ligand binding domain.
Identifieur interne : 000144 ( Main/Exploration ); précédent : 000143; suivant : 000145Differences in activation of aryl hydrocarbon receptors of white sturgeon relative to lake sturgeon are predicted by identities of key amino acids in the ligand binding domain.
Auteurs : Jon A. Doering ; Reza Farmahin [Canada] ; Steve Wiseman ; Shawn C. Beitel ; Sean W. Kennedy [Canada] ; John P. Giesy [Canada] ; Markus Hecker [Canada]Source :
- Environmental science & technology [ 1520-5851 ] ; 2015.
English descriptors
- KwdEn :
- Amino Acids (analysis), Animals, Benzofurans (metabolism), Benzofurans (toxicity), COS Cells, Catalytic Domain, Cercopithecus aethiops, Dibenzofurans, Polychlorinated, Dioxins (metabolism), Endangered Species, Fishes (metabolism), Lakes, Polychlorinated Biphenyls (metabolism), Polychlorinated Biphenyls (toxicity), Polychlorinated Dibenzodioxins (analogs & derivatives), Polychlorinated Dibenzodioxins (metabolism), Polychlorinated Dibenzodioxins (toxicity), Receptors, Aryl Hydrocarbon (chemistry), Receptors, Aryl Hydrocarbon (drug effects), Receptors, Aryl Hydrocarbon (genetics), Species Specificity, Water Pollutants, Chemical (metabolism), Water Pollutants, Chemical (toxicity).
- MESH :
- chemical , analogs & derivatives : Polychlorinated Dibenzodioxins.
- chemical , analysis : Amino Acids.
- chemical , chemistry : Receptors, Aryl Hydrocarbon.
- chemical , drug effects : Receptors, Aryl Hydrocarbon.
- chemical , genetics : Receptors, Aryl Hydrocarbon.
- chemical , metabolism : Benzofurans, Dioxins, Polychlorinated Biphenyls, Polychlorinated Dibenzodioxins, Water Pollutants, Chemical.
- chemical , toxicity : Benzofurans, Polychlorinated Biphenyls, Polychlorinated Dibenzodioxins, Water Pollutants, Chemical.
- metabolism : Fishes.
- Animals, COS Cells, Catalytic Domain, Cercopithecus aethiops, Dibenzofurans, Polychlorinated, Endangered Species, Lakes, Species Specificity.
Abstract
Dioxin-like compounds (DLCs) are pollutants of global environmental concern. DLCs elicit their adverse outcomes through activation of the aryl hydrocarbon receptor (AhR). However, there is limited understanding of the mechanisms that result in differences in sensitivity to DLCs among different species of fishes. Understanding these mechanisms is critical for protection of the diversity of fishes exposed to DLCs, including endangered species. This study investigated specific mechanisms that drive responses of two endangered fishes, white sturgeon (Acipenser transmontanus) and lake sturgeon (Acipenser fulvescens) to DLCs. It determined whether differences in sensitivity to activation of AhRs (AhR1 and AhR2) can be predicted based on identities of key amino acids in the ligand binding domain (LBD). White sturgeon were 3- to 30-fold more sensitive than lake sturgeon to exposure to 5 different DLCs based on activation of AhR2. There were no differences in sensitivity between white sturgeon and lake sturgeon based on activation of AhR1. Adverse outcomes as a result of exposure to DLCs have been shown to be mediated through activation of AhR2, but not AhR1, in all fishes studied to date. This indicates that white sturgeon are likely to have greater sensitivity in vivo relative to lake sturgeon. Homology modeling and in silico mutagenesis suggests that differences in sensitivity to activation of AhR2 result from differences in key amino acids at position 388 in the LBD of AhR2 of white sturgeon (Ala-388) and lake sturgeon (Thr-388). This indicates that identities of key amino acids in the LBD of AhR2 could be predictive of both in vitro activation by DLCs and in vivo sensitivity to DLCs in these, and potentially other, fishes.
DOI: 10.1021/acs.est.5b00085
PubMed: 25761200
Affiliations:
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Le document en format XML
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Doering</name></author><author><name sortKey="Farmahin, Reza" sort="Farmahin, Reza" uniqKey="Farmahin R" first="Reza" last="Farmahin">Reza Farmahin</name><affiliation wicri:level="1"><nlm:affiliation>§Environment Canada, National Wildlife Research Centre, Ottawa, Ontario K1A 0H3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>§Environment Canada, National Wildlife Research Centre, Ottawa, Ontario K1A 0H3</wicri:regionArea><wicri:noRegion>Ontario K1A 0H3</wicri:noRegion></affiliation></author><author><name sortKey="Wiseman, Steve" sort="Wiseman, Steve" uniqKey="Wiseman S" first="Steve" last="Wiseman">Steve Wiseman</name></author><author><name sortKey="Beitel, Shawn C" sort="Beitel, Shawn C" uniqKey="Beitel S" first="Shawn C" last="Beitel">Shawn C. Beitel</name></author><author><name sortKey="Kennedy, Sean W" sort="Kennedy, Sean W" uniqKey="Kennedy S" first="Sean W" last="Kennedy">Sean W. 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Doering</name></author><author><name sortKey="Farmahin, Reza" sort="Farmahin, Reza" uniqKey="Farmahin R" first="Reza" last="Farmahin">Reza Farmahin</name><affiliation wicri:level="1"><nlm:affiliation>§Environment Canada, National Wildlife Research Centre, Ottawa, Ontario K1A 0H3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>§Environment Canada, National Wildlife Research Centre, Ottawa, Ontario K1A 0H3</wicri:regionArea><wicri:noRegion>Ontario K1A 0H3</wicri:noRegion></affiliation></author><author><name sortKey="Wiseman, Steve" sort="Wiseman, Steve" uniqKey="Wiseman S" first="Steve" last="Wiseman">Steve Wiseman</name></author><author><name sortKey="Beitel, Shawn C" sort="Beitel, Shawn C" uniqKey="Beitel S" first="Shawn C" last="Beitel">Shawn C. Beitel</name></author><author><name sortKey="Kennedy, Sean W" sort="Kennedy, Sean W" uniqKey="Kennedy S" first="Sean W" last="Kennedy">Sean W. Kennedy</name><affiliation wicri:level="1"><nlm:affiliation>§Environment Canada, National Wildlife Research Centre, Ottawa, Ontario K1A 0H3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>§Environment Canada, National Wildlife Research Centre, Ottawa, Ontario K1A 0H3</wicri:regionArea><wicri:noRegion>Ontario K1A 0H3</wicri:noRegion></affiliation></author><author><name sortKey="Giesy, John P" sort="Giesy, John P" uniqKey="Giesy J" first="John P" last="Giesy">John P. Giesy</name><affiliation wicri:level="1"><nlm:affiliation>⊥Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B4, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>⊥Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B4</wicri:regionArea><wicri:noRegion>Saskatchewan S7N 5B4</wicri:noRegion></affiliation></author><author><name sortKey="Hecker, Markus" sort="Hecker, Markus" uniqKey="Hecker M" first="Markus" last="Hecker">Markus Hecker</name><affiliation wicri:level="1"><nlm:affiliation>∇School of the Environment and Sustainability, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5C8, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>∇School of the Environment and Sustainability, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5C8</wicri:regionArea><wicri:noRegion>Saskatchewan S7N 5C8</wicri:noRegion></affiliation></author></analytic><series><title level="j">Environmental science & technology</title><idno type="eISSN">1520-5851</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acids (analysis)</term><term>Animals</term><term>Benzofurans (metabolism)</term><term>Benzofurans (toxicity)</term><term>COS Cells</term><term>Catalytic Domain</term><term>Cercopithecus aethiops</term><term>Dibenzofurans, Polychlorinated</term><term>Dioxins (metabolism)</term><term>Endangered Species</term><term>Fishes (metabolism)</term><term>Lakes</term><term>Polychlorinated Biphenyls (metabolism)</term><term>Polychlorinated Biphenyls (toxicity)</term><term>Polychlorinated Dibenzodioxins (analogs & derivatives)</term><term>Polychlorinated Dibenzodioxins (metabolism)</term><term>Polychlorinated Dibenzodioxins (toxicity)</term><term>Receptors, Aryl Hydrocarbon (chemistry)</term><term>Receptors, Aryl Hydrocarbon (drug effects)</term><term>Receptors, Aryl Hydrocarbon (genetics)</term><term>Species Specificity</term><term>Water Pollutants, Chemical (metabolism)</term><term>Water Pollutants, Chemical (toxicity)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Polychlorinated Dibenzodioxins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Amino Acids</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Receptors, Aryl Hydrocarbon</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Receptors, Aryl Hydrocarbon</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Receptors, Aryl Hydrocarbon</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Benzofurans</term><term>Dioxins</term><term>Polychlorinated Biphenyls</term><term>Polychlorinated Dibenzodioxins</term><term>Water Pollutants, Chemical</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Benzofurans</term><term>Polychlorinated Biphenyls</term><term>Polychlorinated Dibenzodioxins</term><term>Water Pollutants, Chemical</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Fishes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>COS Cells</term><term>Catalytic Domain</term><term>Cercopithecus aethiops</term><term>Dibenzofurans, Polychlorinated</term><term>Endangered Species</term><term>Lakes</term><term>Species Specificity</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Dioxin-like compounds (DLCs) are pollutants of global environmental concern. DLCs elicit their adverse outcomes through activation of the aryl hydrocarbon receptor (AhR). However, there is limited understanding of the mechanisms that result in differences in sensitivity to DLCs among different species of fishes. Understanding these mechanisms is critical for protection of the diversity of fishes exposed to DLCs, including endangered species. This study investigated specific mechanisms that drive responses of two endangered fishes, white sturgeon (Acipenser transmontanus) and lake sturgeon (Acipenser fulvescens) to DLCs. It determined whether differences in sensitivity to activation of AhRs (AhR1 and AhR2) can be predicted based on identities of key amino acids in the ligand binding domain (LBD). White sturgeon were 3- to 30-fold more sensitive than lake sturgeon to exposure to 5 different DLCs based on activation of AhR2. There were no differences in sensitivity between white sturgeon and lake sturgeon based on activation of AhR1. Adverse outcomes as a result of exposure to DLCs have been shown to be mediated through activation of AhR2, but not AhR1, in all fishes studied to date. This indicates that white sturgeon are likely to have greater sensitivity in vivo relative to lake sturgeon. Homology modeling and in silico mutagenesis suggests that differences in sensitivity to activation of AhR2 result from differences in key amino acids at position 388 in the LBD of AhR2 of white sturgeon (Ala-388) and lake sturgeon (Thr-388). This indicates that identities of key amino acids in the LBD of AhR2 could be predictive of both in vitro activation by DLCs and in vivo sensitivity to DLCs in these, and potentially other, fishes.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Beitel, Shawn C" sort="Beitel, Shawn C" uniqKey="Beitel S" first="Shawn C" last="Beitel">Shawn C. Beitel</name><name sortKey="Doering, Jon A" sort="Doering, Jon A" uniqKey="Doering J" first="Jon A" last="Doering">Jon A. Doering</name><name sortKey="Wiseman, Steve" sort="Wiseman, Steve" uniqKey="Wiseman S" first="Steve" last="Wiseman">Steve Wiseman</name></noCountry><country name="Canada"><noRegion><name sortKey="Farmahin, Reza" sort="Farmahin, Reza" uniqKey="Farmahin R" first="Reza" last="Farmahin">Reza Farmahin</name></noRegion><name sortKey="Giesy, John P" sort="Giesy, John P" uniqKey="Giesy J" first="John P" last="Giesy">John P. Giesy</name><name sortKey="Hecker, Markus" sort="Hecker, Markus" uniqKey="Hecker M" first="Markus" last="Hecker">Markus Hecker</name><name sortKey="Kennedy, Sean W" sort="Kennedy, Sean W" uniqKey="Kennedy S" first="Sean W" last="Kennedy">Sean W. Kennedy</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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