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 | |
刊名 | AQUATIC TOXICOLOGY |
2018-06-01 | |
卷号 | 199期号:1页码:46-54 |
关键词 | TDCIPP Developmental neurotoxicity Autophagy LC3 II Zebrafish larvae |
ISSN号 | 0166-445X |
DOI | 10.1016/j.aquatox.2018.03.016 |
英文摘要 | Tris (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. |
资助项目 | National Natural Science Foundation of China[21737005] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB14040103] ; State Key Laboratory of Freshwater Ecology and Biotechnology[2016FBZ11] |
WOS关键词 | ORGANOPHOSPHORUS FLAME RETARDANTS ; THYROID ENDOCRINE DISRUPTION ; MAMMALIAN DEVELOPMENT ; PHOSPHATE TDCPP ; MOLECULAR-MECHANISMS ; EXPOSURE ; WATER ; PLASTICIZERS ; EXPRESSION ; TOXICITY |
WOS研究方向 | Marine & Freshwater Biology ; Toxicology |
语种 | 英语 |
出版者 | ELSEVIER SCIENCE BV |
WOS记录号 | WOS:000433271600005 |
资助机构 | National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; 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 ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; 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 ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; 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State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; 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 ; 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National Natural Science Foundation of China ; National Natural Science Foundation of China ; 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 ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; 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 ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; 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内容类型 | 期刊论文 |
源URL | [http://ir.ihb.ac.cn/handle/342005/30403] |
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 | Zhang, Ling; Zhou, Bingsheng |
作者单位 | 1.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 |
推荐引用方式 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(1):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(1),46-54. |
MLA | Li, Ruiwen,et al."A protective role of autophagy in TDCIPP-induced developmental neurotoxicity in zebrafish larvae".AQUATIC TOXICOLOGY 199.1(2018):46-54. |
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