作者： Li, RW (Li, Ruiwen); Zhou, PJ (Zhou, Peijiang); Guo, YY (Guo, Yongyong); Zhou, BS (Zhou, Bingsheng)
来源出版物：NEUROTOXICOLOGY 卷：62页码:14-23 DOI：10.1016/j.neuro.2017.05.002 出版年： SEP 2017
摘要： Exposure and toxicity to organophosphate-based flame retardants are an increasing health concern. Neurons appear to be particularly vulnerable to the effects of these chemicals. For example, in vitro studies have shown that tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) induces apoptosis and autophagy in neural cells. In the present study, we investigated the cell biological mechanisms of TDCIPP-induced neurotoxicity using undifferentiated human SH-SY5Y neuroblastoma cells as a model. Interestingly, TDCIPP treatment promoted differentiation in SH-SY5Y cells, which displayed various alterations including neurite elongation, an expansion of the numbers of neurite-bearing cells, and an increase in expression of cytoskeletal components normally enriched in neurons. Furthermore, the upregulation of microtubule-associated protein light chain 3, the degradation of p62/sequestosome 1, and the formation of autophagosomes occurred in treated cells, suggesting that TDCIPP exposure induces autophagy. However, pretreatment with the autophagy inhibitor 3-methyladenine suppressed TDCIPP-induced autophagy and reduced expression of the aforementioned cytoskeletal components. This correlated with a reduction in neurite outgrowth and numbers of neurite-bearing cells. Taken together, these results indicate that autophagy might promote TDCIPP-induced SH-SY5Y cell differentiation, which leads to an increase in expression of cytoskeletal components and neurite outgrowth. This study offers key insights into the mechanisms of neurotoxicity associated with this commonly used organophosphate.
作者关键词：TDCIPP; SH-SY5Y cells; Differentiation; Cytoskeleton; Autophagy; Neurite outgrowth
扩展关键词： ORGANOPHOSPHORUS FLAME RETARDANTS; ACTIVATED PROTEIN-KINASE; NEURAL STEM-CELLS; NEUROBLASTOMA-CELLS; NEURITE OUTGROWTH; NEURONAL DIFFERENTIATION; MICROTUBULES; NEUROGENESIS; TOXICITY; PATHWAYS
通讯作者地址：Zhou, PJ (reprint author), Wuhan Univ, Hubei Biomass Resource Chem & Environm Biotechnol, Sch Resource & Environm Sci, Wuhan 430079, Hubei, Peoples R China.
Zhou, BS (reprint author), Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Hubei, Peoples R China.
[Li, Ruiwen; Zhou, Peijiang] Wuhan Univ, Hubei Biomass Resource Chem & Environm Biotechnol, Sch Resource & Environm Sci, Wuhan 430079, Hubei, Peoples R China.
[Li, Ruiwen; Guo, Yongyong; Zhou, Bingsheng] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Hubei, Peoples R China.
研究方向： Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology
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