Manganese exposure disrupts SNARE protein complex-mediated vesicle fusion in primary cultured neurons.
Manganese exposure disrupts SNARE protein complex-mediated vesicle fusion in primary cultured neurons.
复制标题
锰暴露会破坏原代培养神经元中 SNARE 蛋白复合物介导的囊泡融合。
DOI：
10.1002/tox.22272
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Xu Zhao-Fa
中科院分区：
文献类型：
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作者：
Wang Can;Xu Bin;Song Qi-Fan;Deng Yu;Liu Wei;Xu Zhao-Fa
众所周知，过度暴露于锰（Mn）会破坏大脑中的神经递质释放。然而，Mn暴露对神经递质囊泡释放的潜在机制尚不清楚。本研究探讨了SNARE复合物相关蛋白的蛋白表达及其相互作用是否是Mn暴露与神经递质囊泡融合障碍之间的媒介。神经元分别暴露于Mn （0 ~ 200 μM）环境0、6、12、18、24 h后，均出现不同程度的细胞损伤。结果表明，在随后的实验中，Mn暴露于100 μM的浓度为0、6、12、18和24 h。Mn可下调培养神经元中SNAP - 25的表达，上调VAMP - 2的表达。此外，Munc - 18与Syntaxin的相互作用在Mn处理18 - 24h后显著增加，VAMP - 2与Synaptophysin的相互作用先增加后降低。FM1‐43标记的突触囊泡也提供了证据，表明Mn处理导致神经递质囊泡融合先增加后减少，这与SNARE复合物的80 kDa蛋白水平一致。研究结果清楚地表明，Mn通过干扰SNARE复合物相关蛋白的表达及其相互作用，诱导神经递质囊泡释放紊乱。©2016 Wiley期刊公司环境科学与技术，2017,31(2):557 - 557。
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.