Reduced level of synapsin I protein in the rat striatum after intraventricular administration of proteasome inhibitors: preliminary studies.
Reduced level of synapsin I protein in the rat striatum after intraventricular administration of proteasome inhibitors: preliminary studies.
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DOI：
10.5603/fm.2015.0103
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发表时间：
2015
影响因子：
1.2
通讯作者：
Sławomir Wójcik;J. Spodnik;J. Sidor-Kaczmarek;Joanna M. Moryś
中科院分区：
文献类型：
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作者：
Sławomir Wójcik;J. Spodnik;J. Sidor-Kaczmarek;Joanna M. Moryś
背景我们最近描述了腹腔内给予MG-132后黑质纹状体末梢的变化，以及脑室内给予MG-132、lactacystin和epoxomicin（不同种类的蛋白酶体抑制剂）后大鼠侧脑室壁的变化。抑制泛素-蛋白酶体系统（UPS）活性的物质由于其作为治疗癌症和脑缺血再灌注损伤的新治疗策略的潜在作用而被深入研究。本研究的目的是确定MG-132、lactacystin和epoxomicin的脑室内给药对大鼠纹状体突触蛋白I水平的影响，突触蛋白I是大脑中最突出的神经元特异性磷蛋白之一。材料、方法和结果在给予所研究的蛋白酶体抑制剂两周后，在大鼠纹状体中观察到突触蛋白I的大量减少（高达80%）。由于神经元，特别是多巴胺能神经元，是敏感的蛋白酶体功能的耗竭，我们假设观察到的突触蛋白I减少可能反映了纹状体神经元和/或黑质纹状体终端的人口的变化。结论对这些结果背后的细胞机制的理解需要进一步的研究，并可能为讨论UPS抑制与神经元存活之间的机制提供有价值的贡献。
BACKGROUND We have recently described changes present in nigrostriatal terminals after intraperitoneal administration of MG-132 and changes that occur in the walls of the rat lateral ventricle after intraventricular administration of MG-132, lactacystin and epoxomicin - different classes of proteasome inhibitors. Substances that inhibit ubiquitin-proteasome system (UPS) activity, are intensively studied due to their potential role as novel therapeutic strategies in the treatment of cancer and ischaemia-reperfusion injury in the brain. The aim of this study is to determine the influence of intraventricular administration of MG-132, lactacystin and epoxomicin on the level in the rat striatum synapsin I - one of the most prominent neuron-specific phosphoproteins in the brain. MATERIALS AND METHODS AND RESULTS Two weeks after administration of studied proteasome inhibitors, substantial reduction (up to 80%) of synapsin I was ob-served in the rat striatum. Because neurons, and especially dopaminergic ones, are sensitive to the depletion of proteasome function, we assume that observed synapsin I decrease may reflect changes in population of striatal neurons and/or nigrostriatal terminals. CONCLUSIONS Understanding of cellular mechanisms standing behind our findings needs further studies, and could provide valuable contribution to the discussion on the mechanisms linking UPS inhibition and survival of neurons.