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.
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Authors | Ding-Xin Long, Dan Hu, Pan Wang, Yi-Jun Wu |
Journal | Molecular and cellular biochemistry
(Mol Cell Biochem)
Vol. 396
Issue 1-2
Pg. 33-40
(Nov 2014)
ISSN: 1573-4919 [Electronic] Netherlands |
PMID | 24990248
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Apoptosis Regulatory Proteins
- BECN1 protein, human
- Beclin-1
- MAP1LC3A protein, human
- Membrane Proteins
- Microtubule-Associated Proteins
- Tritolyl Phosphates
- tri-o-cresyl phosphate
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Topics |
- Apoptosis Regulatory Proteins
(metabolism)
- Autophagy
(drug effects)
- Beclin-1
- Cell Line, Tumor
(drug effects)
- Cytoplasm
(drug effects, ultrastructure)
- Dose-Response Relationship, Drug
- Humans
- Membrane Proteins
(metabolism)
- Microscopy, Electron, Transmission
- Microtubule-Associated Proteins
(genetics, metabolism)
- Neuroblastoma
(drug therapy, metabolism, pathology)
- Neurotoxicity Syndromes
(pathology)
- Phagosomes
(drug effects, ultrastructure)
- Tritolyl Phosphates
(administration & dosage, toxicity)
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