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: 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)

Chemical References

• Apoptosis Regulatory Proteins
• BECN1 protein, human
• Beclin-1
• MAP1LC3A protein, human
• Membrane Proteins
• Microtubule-Associated Proteins
• Tritolyl Phosphates
• tri-o-cresyl phosphate

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)