Tris (1, 3-dichloro-2-propyl) phosphate induces apoptosis and autophagy in SH-SY5Y cells: Involvement of ROS-mediated AMPK/mTOR/ULK1 pathways | |
Li, Ruiwen1,2; Zhou, Peijiang1; Guo, Yongyong2; Lee, Jae-Seong3; Zhou, Bingsheng2 | |
刊名 | FOOD AND CHEMICAL TOXICOLOGY |
2017-02-01 | |
卷号 | 100期号:1页码:183-196 |
关键词 | Tris (1, 3-dichloro-2-propyl) phosphate Autophagy ROS Apoptosis AMPK/mTOR/ULK1 Neurotoxicity |
ISSN号 | 0278-6915 |
DOI | 10.1016/j.fct.2016.12.029 |
英文摘要 | Tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP), an extensively used organophosphorus flame retardant, is frequently detected in the environment and biota. Recent studies have shown that TDCIPP has neurotoxic effects. We hypothesized that the neurotoxicity might occur via the induction of the apoptosis and autophagy pathways. In the present study, we investigated TDCIPP-induced apoptotic death and autophagy in SH-SY5Y cells. Treatment with TDCIPP induced increased reactive oxygen species (ROS) generation and cell apoptosis, as well as autophagy. The autophagy inhibitor 3-methyladenine (3-MA) markedly decreased the expression of the autophagy marker beclin-1, microtubule-associated protein light chain 3-II (LC310, p62/sequestosome 1 (SQSTM1) degradation, and promoted apoptosis. Conversely, the autophagy inducer rapamycin (Rapa) alleviated TDCIPP-induced apoptosis and markedly increased the expression of the autophagy markers. Pretreatment with N-acetyl cysteine (NAC) eliminated the increased ROS generation, resulting in increased cell viability. For further examination of the signaling pathways involved in TDCIPP-induced autophagy, compound C, a pharmacological inhibitor of adenosine monophosphate activated protein kinase (AMPK) was used. Western blotting showed that compound C markedly reduced the expression of phospho-AMPK (p-AMPK) and phospho Unc-51-like kinase 1 (p-ULK1), increased phospho mammalian target of rapamycin (p-mTOR) expression, and decreased beclin-1 and LC3II expression. These results suggested that the AMPK/mTOR/ULK1 signaling pathway was involved in TDCIPP-induced autophagy. The antioxidant NAC antagonized TDCIPP-induced activation of AMPK and autophagy. Taken together, our findings provide the first evidence that TDCIPP promotes apoptosis and autophagy simultaneously and that this process involves the ROS-mediated AlVIPK/mTOR/ULK1 pathways. Lastly, the induction of autophagy is a protective mechanism against TDCIPP-induced apoptosis. (C) 2016 Published by Elsevier Ltd. |
资助项目 | Strategic Priority Research Program of the Chinese Academy of Sciences[XDB14040103] ; National Natural Science Foundation of China[21237005] ; National Natural Science Foundation of China[21577168] |
WOS关键词 | ORGANOPHOSPHATE FLAME RETARDANTS ; ACTIVATED PROTEIN-KINASE ; NEUROBLASTOMA-CELLS ; CROSS-TALK ; MITOCHONDRIAL AUTOPHAGY ; ENDOCRINE DISRUPTION ; INDUCED TOXICITY ; PC12 CELLS ; DEATH ; 3-METHYLADENINE |
WOS研究方向 | Food Science & Technology ; Toxicology |
语种 | 英语 |
出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
WOS记录号 | WOS:000393258300018 |
资助机构 | 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 ; 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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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 ; 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 ; 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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 ; 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 ; 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 ; 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 ; 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内容类型 | 期刊论文 |
源URL | [http://ir.ihb.ac.cn/handle/342005/33066] |
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 | Zhou, Peijiang; Zhou, Bingsheng |
作者单位 | 1.Wuhan Univ, Sch Resource & Environm Sci, Hubei Biomass Resource Chem & Environm Biotechnol, Wuhan 430079, Peoples R China 2.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China 3.Sungkyunkwan Univ, Dept Biol Sci, Coll Sci, Suwon 16419, South Korea |
推荐引用方式 GB/T 7714 | Li, Ruiwen,Zhou, Peijiang,Guo, Yongyong,et al. Tris (1, 3-dichloro-2-propyl) phosphate induces apoptosis and autophagy in SH-SY5Y cells: Involvement of ROS-mediated AMPK/mTOR/ULK1 pathways[J]. FOOD AND CHEMICAL TOXICOLOGY,2017,100(1):183-196. |
APA | Li, Ruiwen,Zhou, Peijiang,Guo, Yongyong,Lee, Jae-Seong,&Zhou, Bingsheng.(2017).Tris (1, 3-dichloro-2-propyl) phosphate induces apoptosis and autophagy in SH-SY5Y cells: Involvement of ROS-mediated AMPK/mTOR/ULK1 pathways.FOOD AND CHEMICAL TOXICOLOGY,100(1),183-196. |
MLA | Li, Ruiwen,et al."Tris (1, 3-dichloro-2-propyl) phosphate induces apoptosis and autophagy in SH-SY5Y cells: Involvement of ROS-mediated AMPK/mTOR/ULK1 pathways".FOOD AND CHEMICAL TOXICOLOGY 100.1(2017):183-196. |
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