title: 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.
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.
authors.forename: Jon A
authors.initials: JA
authors.lastname: Doering
authors.affiliation: §Environment Canada, National Wildlife Research Centre, Ottawa, Ontario K1A 0H3, Canada.|∥Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors.forename: Reza
authors.initials: R
authors.lastname: Farmahin
authors.forename: Steve
authors.initials: S
authors.lastname: Wiseman
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Beitel
authors.affiliation: §Environment Canada, National Wildlife Research Centre, Ottawa, Ontario K1A 0H3, Canada.|∥Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors.forename: Sean W
authors.initials: SW
authors.lastname: Kennedy
authors.affiliation: ⊥Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B4, Canada.
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.affiliation: ∇School of the Environment and Sustainability, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5C8, Canada.
authors.forename: Markus
authors.initials: M
authors.lastname: Hecker
mesh_terms: D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001572:Benzofurans / Q000378:metabolism / Q000633:toxicity; D019556:COS Cells; D020134:Catalytic Domain; D002522:Chlorocebus aethiops; D000072338:Dibenzofurans, Polychlorinated; D004147:Dioxins / Q000378:metabolism; D056727:Endangered Species; D005399:Fishes / Q000378:metabolism*; D060106:Lakes; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D013045:Species Specificity; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*
chemical_list: D000596:Amino Acids; D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D014874:Water Pollutants, Chemical; D011078:Polychlorinated Biphenyls