title: Manganese exposure disrupts SNARE protein complex-mediated vesicle fusion in primary cultured neurons.
abstract: Overexposure to manganese (Mn) has been known to disrupt neurotransmitter release in the brain. However, the underlying mechanisms of Mn exposure on neurotransmitter vesicle release are still unclear. The current study investigated whether the protein expression and their interaction of SNARE complex associated proteins were the media between Mn exposure and neurotransmitter vesicle fusion disorders. After the neurons were respectively exposed to Mn (0-200 μM) for 0, 6, 12, 18, 24 h, there were different degrees of cell injury in neurons. According to the results, Mn exposures in subsequent experiments were restricted to concentrations of 100 μM for 0, 6, 12, 18, 24 h. Mn was found to down-regulate the expression of SNAP-25 and up-regulate the expression of VAMP-2 in cultured neurons. Moreover, the interaction of Munc 18 and Syntaxin increased significantly in response to Mn treatment for 18-24h, and the interaction of VAMP-2 and Synaptophysin increased first and then decreased. FM1-43-labeled synaptic vesicles also provided evidence that the treatment with Mn resulted in neurotransmitter vesicle fusion increasing first and then decreasing, which was consistent with the 80 kDa protein levels of SNARE complexes. The findings clearly demonstrated that Mn induced the disorders of neurotransmitter vesicle release via disturbing the protein expression and their interaction of SNARE complex associated proteins. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 705-716, 2017.
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, People's Republic of China.
authors.forename: Can
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, People's Republic of China.
authors.forename: Qi-Fan
authors.initials: QF
authors.lastname: Song
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, People's Republic of China.
authors.forename: Zhao-Fa
authors.initials: ZF
authors.lastname: Xu
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D005089:Exocytosis; D008345:Manganese / Q000633:toxicity*; D008561:Membrane Fusion / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D061251:Primary Cell Culture; D050765:Qa-SNARE Proteins / Q000378:metabolism; D017208:Rats, Wistar; D050600:SNARE Proteins / Q000378:metabolism*; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D050600:SNARE Proteins; D008345:Manganese
keywords: SNARE protein complex; manganese; neurotoxicity; neurotransmitter vesicle fusion