論文

査読有り
2016年9月

In vitro and in silico evaluation of transactivation potencies of avian AHR1 and AHR2 by endogenous ligands: Implications for the physiological role of avian AHR2

COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
  • In-Sung Kim
  • ,
  • Ji-Hee Hwang
  • ,
  • Masashi Hirano
  • ,
  • Hisato Iwata
  • ,
  • Eun-Young Kim

187
開始ページ
1
終了ページ
9
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.cbpc.2016.03.011
出版者・発行元
ELSEVIER SCIENCE INC

Aryl hydrocarbon receptor (AHR) is well conserved from invertebrates to vertebrates, and it mediates the toxic effects of exogenous ligands, including dioxins. Recent studies reported that AHRs activated by endogenous ligands play critical roles in mammalian physiological homeostasis. Avian species possess at least two AHR isoforms (AHR1 and AHR2), which exhibit species-and isoform-specific transactivation potencies to exogenous ligands, whereas mammals possess a single AHR. To delineate the profiles and roles of endogenous ligands for avian AHR isoforms, we investigated in vitro transactivation potencies of avian AHRs (AHR1 and AHR2 from the jungle crow, Corvus macrorhynchos; common cormorant, Phalacrocorax carbo; and black-footed albatross, Phoebastria nigripes) treated with the endogenous tryptophan metabolites 6-formylindolo [3,2-b] carbazole (FICZ), L-kynurenine (L-Kyn), kynurenic acid (KYNA), and indoxyl sulfate (IS). Furthermore, we analyzed the binding mode of these ligands to each avian AHR isoform by in silico docking simulations. The EC50 of FICZ (0.009-0.032 nM) was similar regardless of the species or isoform of AHR. The estimated in silico binding mode of FICZ to AHRs was well conserved in both isoforms. The transactivation potencies of avian AHRs to other tryptophan metabolites were 10(5)-10(7) fold lower than those for FICZ, and EC50 values varied in a species and isoform-specific manner. This was consistent with poor conservation of the binding mode of L-Kyn, KYNA, and IS predicted in in silico docking simulations. Our results suggest that in avian species, FICZ is the most potent endogenous AHR ligand, and that AHR1 and AHR2 are physiologically functional. (C) 2016 Published by Elsevier Inc.

リンク情報
DOI
https://doi.org/10.1016/j.cbpc.2016.03.011
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27060260
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000382271200001&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.cbpc.2016.03.011
  • ISSN : 1532-0456
  • eISSN : 1878-1659
  • PubMed ID : 27060260
  • Web of Science ID : WOS:000382271200001

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