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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
2017-02-01
Source PublicationFOOD AND CHEMICAL TOXICOLOGY
ISSN0278-6915
Volume100Pages:183-196
AbstractTris (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.
SubtypeArticle
KeywordTris (1, 3-dichloro-2-propyl) Phosphate Autophagy Ros Apoptosis Ampk/mtor/ulk1 Neurotoxicity
DOI10.1016/j.fct.2016.12.029
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Funding OrganizationStrategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; National Natural Science Foundation of China(21237005 ; National Natural Science Foundation of China(21237005 ; 21577168) ; 21577168) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; National Natural Science Foundation of China(21237005 ; National Natural Science Foundation of China(21237005 ; 21577168) ; 21577168)
Language英语
WOS Research AreaFood Science & Technology ; Toxicology
WOS SubjectFood Science & Technology ; Toxicology
WOS KeywordORGANOPHOSPHATE FLAME RETARDANTS ; ACTIVATED PROTEIN-KINASE ; NEUROBLASTOMA-CELLS ; CROSS-TALK ; MITOCHONDRIAL AUTOPHAGY ; ENDOCRINE DISRUPTION ; INDUCED TOXICITY ; PC12 CELLS ; DEATH ; 3-METHYLADENINE
WOS IDWOS:000393258300018
Funding OrganizationStrategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; National Natural Science Foundation of China(21237005 ; National Natural Science Foundation of China(21237005 ; 21577168) ; 21577168) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14040103) ; National Natural Science Foundation of China(21237005 ; National Natural Science Foundation of China(21237005 ; 21577168) ; 21577168)
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/28947
Collection水环境工程研究中心
Affiliation1.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
Recommended Citation
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,2017,100:183-196.
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,100,183-196.
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(2017):183-196.
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