Identification of Molecular Targets for 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) in Teleosts : New Insight into Mechanism of Toxicity

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

17 Scopus Citations
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Author(s)

  • Lianguo Chen
  • Chenyan Hu
  • Bingsheng Zhou
  • Pei-yuan Qian

Detail(s)

Original languageEnglish
Pages (from-to)1840-1847
Journal / PublicationEnvironmental Science and Technology
Volume51
Issue number3
Online published27 Dec 2016
Publication statusPublished - 7 Feb 2017

Abstract

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 (Gα), 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 Gα 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 Gα 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.

Research Area(s)

  • MEDAKA ORYZIAS-MELASTIGMA, ANTIFOULING COMPOUND BUTENOLIDE, CHRONIC EXPOSURE, RISK-ASSESSMENT, SEA-URCHIN, RECEPTOR, PATHWAY, GNRH, PITUITARY, EXPRESSION

Citation Format(s)

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, Lianguo; Au, Doris W. T.; Hu, Chenyan; Peterson, Drew R.; Zhou, Bingsheng; Qian, Pei-yuan.

In: Environmental Science and Technology, Vol. 51, No. 3, 07.02.2017, p. 1840-1847.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review