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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Proteomic analysis of expression and protein interactions in a 6-hydroxydopamine-induced rat brain lesion model.
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Proteomic analysis of expression and protein interactions in a 6-hydroxydopamine-induced rat brain lesion model.

机译：在6-羟基多巴胺诱导的大鼠脑损伤模型中表达和蛋白质相互作用的蛋白质组学分析。

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Parkinson's disease (PD) is the second most common neurodegenerative disorder caused by selective degeneration of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Although mitochondrial abnormality, oxidative stress and proteasomal dysfunction are recognized as major contributors to the progression of PD, there is a limited understanding of the key molecular events that provoke degeneration of DA neurons. Using a proteomic approach, we attempted to identify profiles of proteins with altered expression levels in rats following unilateral stereotaxic injection of 6-hydroxydopamine into the SNc. Protein expression profiles of these proteins in the substantia nigra and the striatum were made using two-dimensional gel electrophoresis in conjunction with a mass spectrometry. More than 70 identified proteins displayed significant differences in their temporal and spatial expression pattern between experimental and vehicle-operated control groups. Based on the identity of the proteins, we further searched for potential binding partners using biological databases available on the web and constructed a protein interaction network. Among several interconnected proteins in the network, we verified the interaction between prohibitin and the NADH-ubiquinone oxidoreductase 30kDa subunit (NDUFS3 subunit; a mitochondrial complex I subunit) by co-immunoprecipitation. We also confirmed, using immunohistochemical localization, that both prohibitin and the NDUFS3 subunit were increased in the dying DA neurons, suggesting its potential role in regulating mitochondrial function in dying DA neurons. Furthermore, knockdown of prohibitin accelerated 6-hydroxydopamine-induced cell death in SH-SY5Y cells. Our results raise the possibility that interconnected proteins in the network may positively or negatively impact the progression of DA neuronal death.
机译：帕金森氏病（PD）是第二种最常见的神经退行性疾病，由黑质致密部（SNc）中的多巴胺能（DA）神经元选择性变性引起。尽管线粒体异常，氧化应激和蛋白酶体功能障碍被认为是PD病情发展的主要因素，但对引起DA神经元变性的关键分子事件的认识有限。使用蛋白质组学方法，我们试图在将6-羟基多巴胺单侧立体定位注入SNc后，鉴定大鼠中表达水平改变的蛋白质的概况。这些蛋白质在黑质和纹状体中的蛋白质表达谱是通过二维凝胶电泳结合质谱法绘制的。超过70种已鉴定的蛋白质在实验组和载体对照组之间的时间和空间表达模式上显示出显着差异。基于蛋白质的身份，我们使用网络上可用的生物学数据库进一步搜索了潜在的结合伴侣，并构建了蛋白质相互作用网络。在网络中的几个相互连接的蛋白质中，我们通过共免疫沉淀法验证了禁止素和NADH-泛醌氧化还原酶30kDa亚基（NDUFS3亚基;线粒体复合体I亚基）之间的相互作用。我们还使用免疫组织化学定位方法证实，垂死的DA神经元中禁止素和NDUFS3亚基均增加，表明其在垂死的DA神经元中调节线粒体功能的潜在作用。此外，抑制素的抑制加速了SH-SY5Y细胞中6-羟基多巴胺诱导的细胞死亡。我们的结果提出了网络中相互连接的蛋白质可能对DA神经元死亡进程产生正面或负面影响的可能性。

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