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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
2017-02-07
Source PublicationENVIRONMENTAL SCIENCE & TECHNOLOGY
ISSN0013-936X
Volume51Issue:3Pages:1840-1847
AbstractEnvironmental 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.
SubtypeArticle
DOI10.1021/acs.est.6b05523
WOS HeadingsScience & Technology ; Technology ; Life Sciences & Biomedicine
Indexed BySCI
Funding OrganizationNatural Science Foundation of China(41576140) ; Natural Science Foundation of China(41576140) ; China Ocean Mineral Resources Research and Development Association(COMR-RDA12SC01) ; China Ocean Mineral Resources Research and Development Association(COMR-RDA12SC01) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Natural Science Foundation of China(41576140) ; Natural Science Foundation of China(41576140) ; China Ocean Mineral Resources Research and Development Association(COMR-RDA12SC01) ; China Ocean Mineral Resources Research and Development Association(COMR-RDA12SC01) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103)
Language英语
WOS Research AreaEngineering ; Environmental Sciences & Ecology
WOS SubjectEngineering, Environmental ; Environmental Sciences
WOS KeywordMEDAKA ORYZIAS-MELASTIGMA ; ANTIFOULING COMPOUND BUTENOLIDE ; CHRONIC EXPOSURE ; RISK-ASSESSMENT ; SEA-URCHIN ; RECEPTOR ; PATHWAY ; GNRH ; PITUITARY ; EXPRESSION
WOS IDWOS:000393738700095
Funding OrganizationNatural Science Foundation of China(41576140) ; Natural Science Foundation of China(41576140) ; China Ocean Mineral Resources Research and Development Association(COMR-RDA12SC01) ; China Ocean Mineral Resources Research and Development Association(COMR-RDA12SC01) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Natural Science Foundation of China(41576140) ; Natural Science Foundation of China(41576140) ; China Ocean Mineral Resources Research and Development Association(COMR-RDA12SC01) ; China Ocean Mineral Resources Research and Development Association(COMR-RDA12SC01) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103)
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/28949
Collection水环境工程研究中心
Affiliation1.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
Recommended Citation
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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