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A protective role of autophagy in TDCIPP-induced developmental neurotoxicity in zebrafish larvae
Li, Ruiwen1,2,3; Zhang, Ling1,2; Shi, Qipeng3; Guo, Yongyong3; Zhang, Wei4; Zhou, Bingsheng3
2018-06-01
Source PublicationAQUATIC TOXICOLOGY
ISSN0166-445X
Volume199Pages:46-54
AbstractTris (1, 3-dichloro-2-propyl) phosphate (TDCIPP), an extensively used organophosphorus flame retardant, is frequently detected in various environmental media and biota, and has been demonstrated as neurotoxic. Autophagy has been proposed as a protective mechanism against toxicant-induced neurotoxicity. The purpose of the present study was to investigate the effect of TDCIPP exposure on autophagy, and its role in TDCIPP-induced developmental neurotoxicity. Zebrafish embryos (2-120 h post-fertilization [hpf]) were exposed to TDCIPP (0, 5, 50 and 500 mu g/l) and a model neurotoxic chemical, chlorpyrifos (CPF, 100 mu g/l). The developmental endpoints, locomotive behavior, cholinesterase activities, gene and protein expression related to neurodevelopment and autophagy were measured in the larvae. Our results demonstrate that exposure to TDCIPP (500 mu g/l) and CPF causes developmental toxicity, including reduced hatching and survival rates and increased malformation rate (e.g., spinal curvature), as well as altered locomotor behavior. The expression of selected neurodevelopmental gene and protein markers (e.g., mbp, syn2a, and alpha 1-tubulitt) was significantly down-regulated in CPF and TDCIPP exposed zebrafish larvae. Treatment with CPF significantly inhibits AChE and BChE, while TDCIPP (0-500 mu g/l) exerts no effects on these enzymes. Furthermore, the conversion of microtubule-associated protein I (LC3 I) to LC3 II was significantly increased in TDCIPP exposed zebrafish larvae. In addition, exposure to TDCIPP also activates transcription of several critical genes in autophagy (e.g. Becn1, atg3, atg5, map1lc3b and sqstm1). To further investigate the role of autophagy in TDCIPP induced developmental neurotoxicity, an autophagy inducer (rapamycin, Rapa, 1 nM) and inhibitor (chloroquine, CQ, 1 mu M) were used. The results demonstrate that the hatching rate, survival rate, and the expression of mbp and a1-tubulin proteins were all significantly increased in larvae treated with TDCIPP (500 mu g/l) and Rapa compared to TDCIPP alone. In contrast, co-treatment with the autophagy inhibitor CQ results in exacerbated neurodevelopmental toxicity. Taken together, our results confirm that exposure to TDCIPP induces autophagy, which plays a protective role in TDCIPP-induced developmental neurotoxicity in zebrafish embryos and larvae.
SubtypeArticle
KeywordTdcipp Developmental Neurotoxicity Autophagy Lc3 Ii Zebrafish Larvae
DOI10.1016/j.aquatox.2018.03.016
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Funding OrganizationNational Natural Science Foundation of China(21737005) ; National Natural Science Foundation of China(21737005) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; State Key Laboratory of Freshwater Ecology and Biotechnology(2016FBZ11) ; State Key Laboratory of Freshwater Ecology and Biotechnology(2016FBZ11) ; National Natural Science Foundation of China(21737005) ; National Natural Science Foundation of China(21737005) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; State Key Laboratory of Freshwater Ecology and Biotechnology(2016FBZ11) ; State Key Laboratory of Freshwater Ecology and Biotechnology(2016FBZ11)
Language英语
WOS Research AreaMarine & Freshwater Biology ; Toxicology
WOS SubjectMarine & Freshwater Biology ; Toxicology
WOS KeywordORGANOPHOSPHORUS FLAME RETARDANTS ; THYROID ENDOCRINE DISRUPTION ; MAMMALIAN DEVELOPMENT ; PHOSPHATE TDCPP ; MOLECULAR-MECHANISMS ; EXPOSURE ; WATER ; PLASTICIZERS ; EXPRESSION ; TOXICITY
WOS IDWOS:000433271600005
Funding OrganizationNational Natural Science Foundation of China(21737005) ; National Natural Science Foundation of China(21737005) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; State Key Laboratory of Freshwater Ecology and Biotechnology(2016FBZ11) ; State Key Laboratory of Freshwater Ecology and Biotechnology(2016FBZ11) ; National Natural Science Foundation of China(21737005) ; National Natural Science Foundation of China(21737005) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; State Key Laboratory of Freshwater Ecology and Biotechnology(2016FBZ11) ; State Key Laboratory of Freshwater Ecology and Biotechnology(2016FBZ11)
Citation statistics
Cited Times:6[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/50872
Collection水环境工程研究中心
Affiliation1.Wuhan Univ Sci & Technol, Sch Publ Hlth, Dept Nutr & Toxicol, Wuhan, Hubei, Peoples R China
2.Wuhan Univ Sci & Technol, Hubei Prov Key Lab Occupat Hazard Identificat & C, Wuhan, Hubei, Peoples R China
3.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Hubei, Peoples R China
4.East China Univ Sci & Technol, Sch Resource & Environm Engn, State Environm Protect Key Lab Environm Risk Asse, Shanghai 200237, Peoples R China
Recommended Citation
GB/T 7714
Li, Ruiwen,Zhang, Ling,Shi, Qipeng,et al. A protective role of autophagy in TDCIPP-induced developmental neurotoxicity in zebrafish larvae[J]. AQUATIC TOXICOLOGY,2018,199:46-54.
APA Li, Ruiwen,Zhang, Ling,Shi, Qipeng,Guo, Yongyong,Zhang, Wei,&Zhou, Bingsheng.(2018).A protective role of autophagy in TDCIPP-induced developmental neurotoxicity in zebrafish larvae.AQUATIC TOXICOLOGY,199,46-54.
MLA Li, Ruiwen,et al."A protective role of autophagy in TDCIPP-induced developmental neurotoxicity in zebrafish larvae".AQUATIC TOXICOLOGY 199(2018):46-54.
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