Aberrant expression of cytoskeleton proteins in hippocampus from patients with mesial temporal lobe epilepsy
Aberrant expression of cytoskeleton proteins in hippocampus from patients with mesial temporal lobe epilepsy
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DOI：
10.1007/s00726-005-0281-y
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发表时间：
2006-04
期刊：
影响因子：
3.5
通讯作者：
Jae-Won Yang;Thomas Czech;M. Felizardo;C. Baumgartner;Gert Lubec
中科院分区：
文献类型：
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作者：
Jae-Won Yang;Thomas Czech;M. Felizardo;C. Baumgartner;Gert Lubec
内侧颞叶癫痫（MTLE）是最常见的癫痫形式，其特征在于细胞结构异常，包括海马神经元细胞丢失和反应性胶质增生。通过蛋白质组学技术确定异常的细胞骨架蛋白表达可能有助于理解仍然难以捉摸的病理机制。我们搜索的差异表达的海马蛋白质的分析方法的基础上，二维凝胶电泳（2-DE）加上质谱明确识别77个蛋白质分析在8个控制和8个MTLE海马CAMPI。对蛋白质进行定量，我们观察到18种蛋白质在MTLE中发生了改变。MTLE中细胞骨架蛋白微管蛋白α 1链、β微管蛋白、profilin Ⅱ、神经元原调节蛋白明显减少，缺失一个肌动蛋白点，而ezrin和vinculin明显增加。在MTLE中改变了几类蛋白质，例如抗氧化蛋白（过氧化物酶3和6）、伴侣蛋白（T复合蛋白1-α、应激诱导磷蛋白1）、信号蛋白MAP激酶激酶1、突触体蛋白（突触结合蛋白I、α-突触核蛋白）、NAD依赖性脱乙酰酶sirtuin-2和26 S蛋白酶调节亚基7蛋白、神经元特异性septin 3。两者合计，研究结果可能代表或导致细胞骨架损伤;异常的抗氧化蛋白，伴侣蛋白，MAP激酶激酶1和NAD依赖性脱乙酰酶sirtuin-2可能参与发病机制，突触体蛋白表达的改变可能反映了MTLE的突触损伤。
Mesial temporal lobe epilepsy (MTLE), the most common form of epilepsy, is characterised by cytoarchitectural abnormalities including neuronal cell loss and reactive gliosis in hippocampus. Determination of aberrant cytoskeleton protein expression by proteomics techniques may help to understand pathomechanism that is still elusive. We searched for differential expression of hippocampal proteins by an analytical method based on two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry unambiguously identifying 77 proteins analysed in eight control and eight MTLE hippocampi. Proteins were quantified and we observed 18 proteins that were altered in MTLE. Cytoskeleton proteins tubulin α-1 chain, β-tubulin, profilin II, neuronal tropomodulin were significantly reduced and one actin spot was missing, whereas ezrin and vinculin were significantly increased in MTLE. Proteins of several classes as e.g. antioxidant proteins (peroxiredoxins 3 and 6), chaperons (T-complex protein 1-α, stress-induced-phosphoprotein 1), signaling protein MAP kinase kinase 1, synaptosomal proteins (synaptotagmin I, α-synuclein), NAD-dependent deacetylase sirtuin-2 and 26S protease regulatory subunit 7 protein, neuronal-specific septin 3 were altered in MTLE. Taken together, the findings may represent or lead to cytoskeletal impairment; aberrant antioxidant proteins, chaperons, MAP kinase kinase 1 and NAD-dependent deacetylase sirtuin-2 may have been involved in pathogenetic mechanisms and altered synaptosomal protein expression possibly reflects synaptic impairment in MTLE.