The involvement of autophagy and cytoskeletal regulation in TDCIPP-induced SH-SY5Y cell differentiation.

Neurotoxicology
Ruiwen LiBingsheng Zhou

Abstract

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 n...Continue Reading

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Citations

Jun 15, 2018·Oncotarget·Marzia OgnibeneAnnalisa Pezzolo
Jun 13, 2020·Critical Reviews in Toxicology·Deepika DeepikaVikas Kumar
Sep 16, 2019·Environmental Science and Pollution Research International·Simin WangXueyan Li

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