Yang J W, Czech T, Felizardo M, Baumgartner C, Lubec G
Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
Amino Acids. 2006 Jun;30(4):477-93. doi: 10.1007/s00726-005-0281-y. Epub 2006 Apr 4.
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 alpha-1 chain, beta-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-alpha, stress-induced-phosphoprotein 1), signaling protein MAP kinase kinase 1, synaptosomal proteins (synaptotagmin I, alpha-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.
内侧颞叶癫痫(MTLE)是最常见的癫痫类型,其特征是细胞结构异常,包括海马体中的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不清楚的发病机制。我们采用基于二维凝胶电泳(2-DE)结合质谱的分析方法,寻找海马体蛋白的差异表达,明确鉴定了在8个对照海马体和8个MTLE海马体中分析的77种蛋白质。对蛋白质进行了定量分析,我们观察到18种蛋白质在MTLE中发生了改变。细胞骨架蛋白微管蛋白α-1链、β-微管蛋白、丝切蛋白II、神经元原肌球蛋白显著减少,一个肌动蛋白斑点缺失,而埃兹蛋白和纽蛋白在MTLE中显著增加。几类蛋白质,如抗氧化蛋白(过氧化物酶3和6)、伴侣蛋白(T复合物蛋白1-α、应激诱导磷蛋白1)、信号蛋白丝裂原活化蛋白激酶激酶1、突触体蛋白(突触结合蛋白I、α-突触核蛋白)、NAD依赖性脱乙酰酶沉默调节蛋白2和26S蛋白酶调节亚基7蛋白、神经元特异性septin 3在MTLE中发生了改变。综上所述,这些发现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、丝裂原活化蛋白激酶激酶1和NAD依赖性脱乙酰酶沉默调节蛋白2可能参与了发病机制,突触体蛋白表达的改变可能反映了MTLE中的突触损伤。