title: Proteomic changes in brain tissues of marine medaka (Oryzias melastigma) after chronic exposure to two antifouling compounds: butenolide and 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT).
abstract: SeaNine 211 with active ingredient of 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) has been used as a "green" antifouling agent worldwide but has raised serious biosafety concerns in coastal environments. DCOIT has the potential to disrupt the neurotransmission in nervous system, but the underlying mechanism has not been clarified. In the present study, we used TMT six-plex labeling coupled with two-dimensional LC-MS/MS analysis to investigate the protein expression profiles in brain tissues of the marine medaka (Oryzias melastigma) after a 28-day exposure to environmentally-realistic concentration of DCOIT at 2.55 μg/L (0.009 μM) or butenolide, one promising antifouling compound, at 2.31 μg/L (0.012 μM). DCOIT and butenolide induced differential expression of 26 and 18 proteins in male brains and of 27 and 23 proteins in female brains, respectively. Distinct mechanisms of toxicity were initiated by DCOIT and butenolide in males, whereas the protein expression profiles were largely similar in females treated by these two compounds. In males, DCOIT exposure mainly led to disruption of mitogen-activated protein kinase (MAPK) signaling pathway, while butenolide affected proteins related to the cytoskeletal disorganization that is considered as a general response to toxicant stress. Furthermore, a sex-dependent protein expression profile was also noted between male and female fish, as evident by the inverse changes in the expressions of common proteins (5 proteins for butenolide- and 2 proteins for DCOIT-exposed fish). Overall, this study provided insight into the molecular mechanisms underlying the toxicity of DCOIT and butenolide. The extremely low concentrations used in this study highlighted the ecological relevance, arguing for thorough assessments of their ecological risks before the commercialization of any new antifouling compound.
authors.affiliation: Division of Life Science and Environmental Science Programs, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Lianguo
authors.initials: L
authors.lastname: Chen
authors.affiliation: Biosciences Core Laboratory, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
authors.forename: Huoming
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Division of Life Science and Environmental Science Programs, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Yue-Him
authors.initials: YH
authors.lastname: Wong
authors.affiliation: Division of Life Science and Environmental Science Programs, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Han
authors.affiliation: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong, China.
authors.forename: Doris W T
authors.initials: DW
authors.lastname: Au
authors.affiliation: Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Bajic
authors.affiliation: Division of Life Science and Environmental Science Programs, Hong Kong University of Science and Technology, Hong Kong, China. Electronic address: boqianpy@ust.hk.
authors.forename: Pei-Yuan
authors.initials: PY
authors.lastname: Qian
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000187:drug effects*; D004781:Environmental Exposure; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009990:Oryzias / Q000502:physiology*; D040901:Proteomics; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D013844:Thiazoles; D014874:Water Pollutants, Chemical; C080469:Kathon 930; C004511:butenolide; D020928:Mitogen-Activated Protein Kinases; D015107:4-Butyrolactone
keywords: Brain neurotoxicity; Butenolide; DCOIT; Gender difference; Marine medaka; Proteome