Inhibition of Calpains Protects Mn-Induced Neurotransmitter release disorders in Synaptosomes from Mice: Involvement of SNARE Complex and Synaptic Vesicle Fusion.
Inhibition of Calpains Protects Mn-Induced Neurotransmitter release disorders in Synaptosomes from Mice: Involvement of SNARE Complex and Synaptic Vesicle Fusion.
复制标题
抑制钙蛋白酶可保护小鼠突触体中锰诱导的神经递质释放障碍：SNARE 复合体和突触小泡融合的参与
DOI：
10.1038/s41598-017-04017-9
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发表时间：
2017-06-16
影响因子：
4.6
通讯作者：
Xu ZF
中科院分区：
文献类型：
--
作者：
Wang C;Xu B;Ma Z;Liu C;Deng Y;Liu W;Xu ZF
过度接触锰 (Mn) 可能会通过影响 SNARE 复合体的形成来破坏神经递质的释放，但其潜在机制仍不清楚。先前的研究表明SNAP-25是钙蛋白酶的底物之一。目前的研究调查了钙蛋白酶是否参与了锰诱导的 SNARE 复合体紊乱。小鼠接受Mn处理24天后，Mn处理组和calpeptin预处理组基底核中Mn沉积显着增加。在行为上，在暴露 24 天的锰后，在旷场测试中，在该区域中心花费的时间减少，平均速度显着降低。随着MnCl2剂量的增加，细胞内Ca2+显着增加，但钙肽预处理导致钙蛋白酶活性呈剂量依赖性下降。 Mn处理组中出现SNAP-25蛋白N端片段，但随着calpeptin预处理而减少。 FM1-43 标记的突触小泡也提供了证据，表明 Mn 处理导致先增加后减少，这与 Glu 释放和 SNARE 复合物的 80 kDa 蛋白质水平一致。综上所述，Mn通过体内钙蛋白酶的过度激活，裂解SNAP-25，影响SNARE复合物的形成，从而导致神经递质释放紊乱。
Overexposure to manganese (Mn) could disrupt neurotransmitter release via influencing the formation of SNARE complex, but the underlying mechanisms are still unclear. A previous study demonstrated that SNAP-25 is one of substrate of calpains. The current study investigated whether calpains were involved in Mn-induced disorder of SNARE complex. After mice were treated with Mn for 24 days, Mn deposition increased significantly in basal nuclei in Mn-treated and calpeptin pre-treated groups. Behaviorally, less time spent in the center of the area and decreased average velocity significantly in an open field test after 24 days of Mn exposure. With the increase in MnCl2 dosage, intracellular Ca2+ increased significantly, but pretreatment with calpeptin caused a dose-dependent decrease in calpains activity. There were fragments of N-terminal of SNAP-25 protein appearance in Mn-treated groups, but it is decreased with pretreatment of calpeptin. FM1-43-labeled synaptic vesicles also provided evidence that the treatment with Mn resulted in increasing first and then decreasing, which was consistent with Glu release and the 80 kDa protein levels of SNARE complexes. In summary, Mn induced the disorder of neurotransmitter release through influencing the formation of SNARE complex via cleaving SNAP-25 by overactivation of calpains in vivo.