title: Induction of autophagy in human neuroblastoma SH-SY5Y cells by tri-ortho-cresyl phosphate.
abstract: Tri-ortho-cresyl phosphate (TOCP) is an organophosphorus ester and has been widely used in industry. It is found that TOCP induced delayed neurotoxicity in humans and sensitive animal species. However, the mechanism of TOCP-induced neural cytotoxicity remains unclear. In this study, we studied whether autophagy is involved in TOCP-induced neural cytotoxicity in human neuroblastoma SH-SY5Y cells. We found that 0.5 and 1.0 mM TOCP treatment significantly increased the ectopic accumulation of microtubule-associated protein 1 light chain 3 (LC3)-immunopositive puncta, Beclin 1, and LC3-II/LC3-I levels in SH-SY5Y cells in a dose-dependent manner. Notably, by monodansylcadaverine staining method, we found abundant punctate fluorescent acidic vesicular organelles in TOCP-treated cells. Furthermore, ultrastructural observation under the transmission electron microscope indicated that the cytoplasm was occupied by autophagosomes in TOCP-treated SH-SY5Y cells. Thus, these results suggest that TOCP may induce autophagy, and autophagy may be involved in the development of TOCP-induced neural cytotoxicity.
authors.affiliation: Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxi Road, Beijing, 100101, People's Republic of China.
authors.forename: Ding-Xin
authors.initials: DX
authors.lastname: Long
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Wu
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D045744:Cell Line, Tumor / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D020258:Neurotoxicity Syndromes / Q000473:pathology; D010588:Phagosomes / Q000187:drug effects / Q000648:ultrastructure; D014317:Tritolyl Phosphates / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D014317:Tritolyl Phosphates; C025541:tri-o-cresyl phosphate