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Published on: July 30, 2016
Melatonin Protects Neural Stem Cells Against Tri-Ortho-Cresyl Phosphate-Induced Autophagy
Chang Liu1, Wenjuan Zhou1, Zhaopei Li2
1Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Mental Disorders, Department of Anatomy and Histoembryology, School of Basic Medical Sciences, Shandong University, Jinan, China.
Abstract:
Tri-ortho-cresyl phosphate (TOCP) is an extensively used organophosphate in industry. It has been proven to lead to toxicity in different organ systems, especially in the nervous system. Neural stem cells (NSCs) play important roles in both embryonic and adult nervous systems. However, whether TOCP induces cytotoxicity in embryonic NSCs remains unclear. In this study, mouse NSCs were exposed to different concentrations of TOCP for 24 h. The results showed that TOCP led to impaired proliferation of NSCs and induced the autophagy of NSCs by increasing the generation of intracellular reactive oxygen species (ROS) and decreasing the phosphorylation of extracellular regulated protein kinase (ERK1/2). Melatonin has been reported to exert neuroprotective effects via various mechanisms. Therefore, we further investigate whether melatonin has potential protective effects against TOCP-induced cytotoxicity on NSCs. Our data showed that melatonin pretreatment attenuated TOCP-induced autophagy by suppressing oxidative stress and restoring ERK1/2 phosphorylation consistently. Taken together, the results indicated that TOCP induced the autophagy in mouse NSCs, and melatonin may effectively protect NSCs against TOCP-induced autophagy.
Insights
Tri-ortho-cresyl phosphate (TOCP) causes neural stem cell (NSC) autophagy via oxidative stress. Melatonin protects NSCs from TOCP-induced autophagy by reducing oxidative stress and restoring ERK1/2 phosphorylation.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Tri-ortho-cresyl phosphate (TOCP) is an industrial organophosphate linked to neurotoxicity.
- Neural stem cells (NSCs) are crucial for nervous system development and repair.
- The impact of TOCP on embryonic NSCs is not well understood.
Purpose of the Study:
- To investigate TOCP's cytotoxicity on mouse NSCs.
- To explore the role of autophagy in TOCP-induced NSC damage.
- To determine melatonin's neuroprotective potential against TOCP effects on NSCs.
Main Methods:
- Mouse NSCs were exposed to varying TOCP concentrations.
- Intracellular reactive oxygen species (ROS) generation and ERK1/2 phosphorylation were measured.
- Autophagy induction and cell proliferation were assessed.
- Melatonin pretreatment effects were evaluated.
Main Results:
- TOCP impaired NSC proliferation and induced autophagy.
- TOCP increased ROS generation and decreased ERK1/2 phosphorylation.
- Melatonin pretreatment suppressed TOCP-induced autophagy.
- Melatonin mitigated oxidative stress and restored ERK1/2 phosphorylation.
Conclusions:
- TOCP induces autophagy in mouse NSCs, mediated by oxidative stress and altered ERK1/2 signaling.
- Melatonin demonstrates neuroprotective effects against TOCP-induced NSC autophagy.
- Melatonin may be a potential therapeutic agent for TOCP-related neurotoxicity.
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