Changes in intracellular protein expression in cortex., thalamus and hippocampus in a genetic rat model of absence epilepsy
Changes in intracellular protein expression in cortex., thalamus and hippocampus in a genetic rat model of absence epilepsy
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DOI：
10.1016/j.brainresbull.2011.02.002
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发表时间：
2011-04-05
影响因子：
3.8
通讯作者：
Ogan, Ayse
中科院分区：
文献类型：
--
作者：
Danis, Ozkan;Demir, Serap;Ogan, Ayse
癫痫是一种慢性疾病，其特征是由于大脑神经元异常激活而导致反复癫痫发作。尽管与 Na+、K+、Ca2+ 通道相关的基因突变已被确定，但很少有研究表明细胞内蛋白质发生变化。我们利用蛋白质组学研究了失神性癫痫遗传大鼠模型“斯特拉斯堡遗传性失神性癫痫大鼠（GAERS）”中可溶性蛋白的表达。该技术的优点是在给定时间对所有蛋白质及其翻译后修饰进行高通量定量和定性检测。从 GAERS 和非癫痫对照大鼠大脑中解剖出顶叶皮层和丘脑（负责产生失神性癫痫发作的区域）以及不参与此活动的海马体。通过二维凝胶电泳分离和分离来自每个组织样品的蛋白质。通过 Nano LC-ESI-MS/MS 鉴定了对照和 GAERS 之间表达水平显着不同的斑点。已鉴定的蛋白质为： 顶叶皮层中的 ATP 合酶亚基 delta 和 14-3-3 zeta 亚型；丘脑髓磷脂碱性蛋白和巨噬细胞迁移抑制因子；以及海马巨噬细胞迁移抑制因子和0-β2球蛋白。除 0-β 球蛋白外，GAERS 中所有蛋白表达均上调。这些可溶性蛋白质与能量产生、信号转导、炎症过程和膜电导有关。这些结果表明，不仅膜蛋白而且细胞质蛋白也可能发生在病理生理学中，并且可以成为失神性癫痫的治疗靶点。 (C) 2011 Elsevier Inc. 保留所有权利。
Epilepsy is a chronic disorder characterized by repeated seizures resulting from abnormal activation of neurons in the brain. Although mutations in genes related to Na+, K+, Ca2+ channels have been defined, few studies show intracellular protein changes. We have used proteomics to investigate the expression of soluble proteins in a genetic rat model of absence epilepsy "Genetic Absence Epilepsy Rats from Strasbourg (GAERS)". The advantage of this technique is its high throughput quantitative and qualitative detection of all proteins with their post-translational modifications at a given time. The parietal cortex and thalamus, which are the regions responsible for the generation of absence seizures, and the hippocampus, which is not involved in this activity, were dissected from GAERS and from non-epileptic control rat brains. Proteins from each tissue sample were isolated and separated by two-dimensional gel electrophoresis. Spots that showed significantly different levels of expression between controls and GAERS were identified by nano LC-ESI-MS/MS. Identified proteins were: ATP synthase subunit delta and the 14-3-3 zeta isoform in parietal cortex; myelin basic protein and macrophage migration inhibitory factor in thalamus; and macrophage migration inhibitory factor and 0-beta 2 globulin in hippocampus. All protein expressions were up-regulated in GAERS except 0-beta globulin. These soluble proteins are related to energy generation, signal transduction, inflammatory processes and membrane conductance. These results indicate that not only membrane proteins but also cytoplasmic proteins may take place in the pathophysiology and can be therapeutic targets in absence epilepsy. (C) 2011 Elsevier Inc. All rights reserved.