Measured and predicted affinities of binding and relative potencies to activate the AhR of PAHs and their alkylated analogues SCIE SCOPUS

Cited 25 time in WEB OF SCIENCE Cited 25 time in Scopus
Title
Measured and predicted affinities of binding and relative potencies to activate the AhR of PAHs and their alkylated analogues
Author(s)
Lee, Sangwoo; Shin, Woong-Hee; Hong, Seongjin; Kang, Habyeong; Jung, Dawoon; Yim, Un Hyuk; Shim, Won Joon; Khim, Jong Seong; Seok, Chaok; Giesy, John P.; Choi, Kyungho
KIOST Author(s)
Yim, Un Hyuk(임운혁)Shim, Won Joon(심원준)
Publication Year
2015-11
Abstract
Polycyclic aromatic hydrocarbons (PM-Is) and their alkylated forms are important components of crude oil. Both groups of PAHs have been reported to cause dioxin-like responses, mediated by aryl hydrocarbon receptor (AhR). Thus, characterization of binding affinity to the AhR of unsubstituted or alkylated PAHs is important to understand the toxicological consequences of oil contamination on ecosystems. We investigated the potencies of major PAHs of crude oil, e.g., chrysene, phenanthrene and dibenzothiophene, and their alkylated forms (n = 17) to upregulate expression of AhR-mediated processes by use of the H4IIE-luc transactivation bioassay. In addition, molecular descriptors of different AhR activation potencies among PAHs were investigated by use of computational molecular docking models. Based on responses of the H411E-luc in vitro assay, it was shown that potencies of PAHs were determined by alkylation in addition to the number and conformation of rings. Potencies of AhR-mediated processes were generally greater when a chrysene group was substituted, especially in 1-methyl-chrysene. Significant negative correlations were observed between the in vitro dioxin-like potency measured in H4IIE-hic cells and the binding distance estimated from the in silica modeling. The difference in relative potency for AhR activation observed among PAHs and their alkylated forms could be explained by differences among binding distances in the ligand binding domain of the AhR caused by alkylation. The docking model developed in the present study may have utility in predicting risks of environmental contaminants of which toxicities are mediated by AhR binding. (C) 2015 Elsevier Ltd. All rights reserved.
ISSN
0045-6535
URI
https://sciwatch.kiost.ac.kr/handle/2020.kiost/2385
DOI
10.1016/j.chemosphere.2015.05.033
Bibliographic Citation
CHEMOSPHERE, v.139, pp.23 - 29, 2015
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Subject
POLYCYCLIC AROMATIC-HYDROCARBONS; PROTEIN-LIGAND DOCKING; IN-VITRO; RECEPTOR; IDENTIFICATION; DIOXINS; DIBENZOFURANS; NAPHTHALENES; SENSITIVITY; DERIVATIVES
Keywords
Polycyclic aromatic hydrocarbon; Alkylation; H4IIE-luc; Aryl hydrocarbon receptor; In vitro; Docking model
Type
Article
Language
English
Document Type
Article
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Related Researcher
Research Interests

Microplastic pollution,Persistent Organic Pollutants,Oil Pollution,미세플라스틱 오염,잔류성 유기오염물질,유류오염

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