Aryl hydrocarbon receptor activity of polyhalogenated carbazoles and the molecular mechanism
文献类型：期刊论文
| 作者 | Ma, Dan1; Xie, Heidi Qunhui1; Zhang, Wanglong1; Xue, Qiao1; Liu, Xiuchang1; Xu, Li1; Ma, Yongchao1; Bonefelci-Jorgensen, Eva Cecilie; Long, Manhai2; Zhang, Aiqian1 |
| 刊名 | SCIENCE OF THE TOTAL ENVIRONMENT
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| 出版日期 | 2019-10-15 |
| 卷号 | 687页码:516-526 |
| 关键词 | Polyhalogenated carbazoles Aryl hydrocarbon receptor CH223191 2,3,7,8-tetrachlorodibenzo-p-dioxin Luciferase reporter assay |
| ISSN号 | 0048-9697 |
| 英文摘要 | Polyhalogenated carbazoles (PHCZs) are a class of contaminants identified with persistence and bioaccumulation property from previous studies. However, the toxic effect and mechanism of PHCZs are not fully understood. In this study, eleven PHCZs, including four chlorocarbazoles, four bromocarbazoles and two bromo/chlorocarbazoles were screened for their potential aryl hydrocarbon receptor (AhR) activity by using a dioxin responsive element-driven luciferase reporter assay. We found that nine PHCZs significantly activated AhR in a concentration-dependent manner. Their potencies of AhR activation were 1000 to 100,000 folds less than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent AhR ligand. The relative AhR activation potency of the nine PHCZs followed the order 2,3,6,7-tetrachloro-9H-carbazole >2,7-dibromo-9H-carbazole >1,3,6-tribromo-9H-carbazole >1,3,6,8-tetrachloro-9H-carbazole >1,3,6,8-tetrabromo-9H-carbazole >1-bromo-3,6-dichloro-9H-carbazole >3,6-dibromo-9H-carbazole >3-bromo-9H-carbazole >1,8-dibromo-3,6-dichloro-9H-carbazole, which was partly in line with the induction of AhR-mediated CYP1A1 expression. In silico analysis indicated that the nine PHCZs could be docked into the same pocket as TCDD due to their high structural similarity. However, the shrunk size of the heterocyclic moieties in PHCZs relative to that in TCDD dramatically decreased the complex stability provided by inter-molecular interactions. Moreover, two distinguished docking poses adopted by the nine PHCZs were found, in which one was illustrated by 2367-CCZ and 27-BCZ while the other symbolized by TCDD and the left seven agonists. The differential antagonizing effects of CH223191 on PHCZ-induced AhR activity supported such pose differentiation. The present experimental and in silico data provide new direct evidence of PHCZ-AhR interaction which sheds light on AhR-associated toxicological study and risk assessment of PHCZs. (C) 2019 Published by Elsevier B.V. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/42509]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 作者单位 | 1.Chinese Acad Sci, Res Ctr Ecoenvimnment Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Aarhus Univ, Dept Publ Hlth, Ctr Arctic Hlth & Mol Epidemiol, DK-8000 Aarhus, Denmark |
| 推荐引用方式 GB/T 7714 | Ma, Dan,Xie, Heidi Qunhui,Zhang, Wanglong,et al. Aryl hydrocarbon receptor activity of polyhalogenated carbazoles and the molecular mechanism[J]. SCIENCE OF THE TOTAL ENVIRONMENT,2019,687:516-526. |
| APA | Ma, Dan.,Xie, Heidi Qunhui.,Zhang, Wanglong.,Xue, Qiao.,Liu, Xiuchang.,...&Zhao, Bin.(2019).Aryl hydrocarbon receptor activity of polyhalogenated carbazoles and the molecular mechanism.SCIENCE OF THE TOTAL ENVIRONMENT,687,516-526. |
| MLA | Ma, Dan,et al."Aryl hydrocarbon receptor activity of polyhalogenated carbazoles and the molecular mechanism".SCIENCE OF THE TOTAL ENVIRONMENT 687(2019):516-526. |
入库方式： OAI收割
来源：生态环境研究中心
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