Identification of Molecular Targets for 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) in Teleosts: New Insight into Mechanism of Toxicity | |
Chen, Lianguo1,2; Au, Doris W. T.3; Hu, Chenyan4; Peterson, Drew R.3; Zhou, Bingsheng2; Qian, Pei-Yuan1 | |
刊名 | ENVIRONMENTAL SCIENCE & TECHNOLOGY |
2017-02-07 | |
卷号 | 51期号:3页码:1840-1847 |
ISSN号 | 0013-936X |
DOI | 10.1021/acs.est.6b05523 |
英文摘要 | Environmental pollutants are capable of concomitantly inducing diverse toxic effects. However, it is largely unknown which effects are directly induced and which effects are secondary, thus calling for definitive identification of the initiating molecular event for a pollutant to elucidate the mechanism of toxicity. In the present study, affinity pull-down assays were used to identify target proteins for 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT), a costal pollutant of emerging concern, in various tissues (e.g., brain, liver, plasma, and gonad) from marine medaka (Olyzias melastigma) and zebrafish (Danio rerio). Pull-down results showed that, in male and female brains from medaka and zebrafish, DCOIT had a consistently high affinity for G protein alpha subunits (G alpha), suggesting the targeted effects of DCOIT on signaling transduction from G protein-coupled receptors (GPCRs) and an extrapolatable mode of action in teleost brains. Validation using recombinant proteins and molecular docking analysis confirmed that binding of DCOIT to G alpha protein competitively inhibited its activation by substrate. Considering the involvement of GPCRs in the regulation of myriad biological processes, including the hypothalamus-pituitary-gonadal-liver axis, binding of DCOIT to upstream G alpha proteins in the brain may provide a plausible explanation for the diversity of toxic effects resulting from DCOIT challenge, especially abnormal hormonal production through the mitogen-activated protein kinase pathway. A new mechanism of action based on GPCR signaling is thus hypothesized for endocrine disrupting chemicals and warrants further research to clearly elucidate the link between GPCR signaling and endocrine disruption. |
资助项目 | Natural Science Foundation of China[41576140] ; China Ocean Mineral Resources Research and Development Association[COMR-RDA12SC01] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB14040103] |
WOS关键词 | MEDAKA ORYZIAS-MELASTIGMA ; ANTIFOULING COMPOUND BUTENOLIDE ; CHRONIC EXPOSURE ; RISK-ASSESSMENT ; SEA-URCHIN ; RECEPTOR ; PATHWAY ; GNRH ; PITUITARY ; EXPRESSION |
WOS研究方向 | Engineering ; Environmental Sciences & Ecology |
语种 | 英语 |
出版者 | AMER CHEMICAL SOC |
WOS记录号 | WOS:000393738700095 |
资助机构 | Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; China Ocean Mineral Resources Research and Development Association ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences |
内容类型 | 期刊论文 |
源URL | [http://ir.ihb.ac.cn/handle/342005/33011] |
专题 | 水生生物研究所_水环境工程研究中心_期刊论文 |
通讯作者 | Zhou, Bingsheng; Qian, Pei-Yuan |
作者单位 | 1.Hong Kong Univ Sci & Technol, Div Life Sci, Clear Water Bay, Hong Kong, Peoples R China 2.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China 3.City Univ Hong Kong, Dept Biol & Chem, State Key Lab Marine Pollut, Kowloon, Hong Kong, Peoples R China 4.Wuhan Inst Technol, Sch Chem & Environm Engn, Wuhan 430072, Peoples R China |
推荐引用方式 GB/T 7714 | Chen, Lianguo,Au, Doris W. T.,Hu, Chenyan,et al. Identification of Molecular Targets for 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) in Teleosts: New Insight into Mechanism of Toxicity[J]. ENVIRONMENTAL SCIENCE & TECHNOLOGY,2017,51(3):1840-1847. |
APA | Chen, Lianguo,Au, Doris W. T.,Hu, Chenyan,Peterson, Drew R.,Zhou, Bingsheng,&Qian, Pei-Yuan.(2017).Identification of Molecular Targets for 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) in Teleosts: New Insight into Mechanism of Toxicity.ENVIRONMENTAL SCIENCE & TECHNOLOGY,51(3),1840-1847. |
MLA | Chen, Lianguo,et al."Identification of Molecular Targets for 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) in Teleosts: New Insight into Mechanism of Toxicity".ENVIRONMENTAL SCIENCE & TECHNOLOGY 51.3(2017):1840-1847. |
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