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

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 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.

• Authors: Ruiwen Li, Peijiang Zhou, Yongyong Guo, Bingsheng Zhou
• Journal: Neurotoxicology (Neurotoxicology) Vol. 62 Pg. 14-23 (Sep 2017) ISSN: 1872-9711 [Electronic] Netherlands
• PMID: 28495519 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier B.V.

Chemical References

• Flame Retardants
• MAP1LC3A protein, human
• MAP2 protein, human
• Microtubule-Associated Proteins
• Organophosphorus Compounds
• P62 protein, human
• RNA-Binding Proteins
• Tubulin
• tris(1,3-dichloro-2-propyl)phosphate
• L-Lactate Dehydrogenase

Topics

• Animals
• Autophagy (drug effects)
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cytoskeleton (drug effects, metabolism)
• Dose-Response Relationship, Drug
• Flame Retardants (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• L-Lactate Dehydrogenase (metabolism)
• Microtubule-Associated Proteins (genetics, metabolism)
• Neuroblastoma (pathology)
• Neuronal Outgrowth (drug effects)
• Organophosphorus Compounds (pharmacology)
• RNA-Binding Proteins (genetics, metabolism)
• Time Factors
• Tubulin (genetics, metabolism)