Tau蛋白病的蛋白质组研究  

A preliminary proteomic analysis of tauopathies

作　　者：杨国锋[1] 王鲁宁[1] 纪建国[2] 何思志[2] 朱明伟[1] 王青松[2] 

机构地区：[1]解放军总医院老年神经科,北京100853 [2]北京大学生命科学院蛋白质工程国家重点实验室

出　　处：《中华内科杂志》2005年第5期374-377,共4页Chinese Journal of Internal Medicine

基　　金：全军"十五"重点课题资助项目(01Z037)

摘　　要：目的　对Tau蛋白病患者与4例正常老年人尸检脑标本进行蛋白质组学研究以期了解Tau蛋白病分子机制并寻找诊断治疗该疾病的蛋白质标记物。方法　颞叶蛋白质以固相pH梯度等电聚焦为第一向,SDS PAGE垂直电泳为第二向进行双向电泳(2 DE),分析电泳图谱,基质辅助激光解析/电离飞行时间(MALDI TOF)质谱或MALDI TOF/TOF串联质谱鉴定蛋白质。结果　18种蛋白质的表达量在Tau蛋白病患者与正常老年人显著不同。分别被鉴定为3 磷酸甘油醛脱氢酶、尿嘧啶DNA糖苷水解酶、Cu Zn超氧化物歧化酶、异柠檬酸脱氢酶亚单位、synaptotagminI、Peroxiredoxin2、胶质纤维酸性蛋白、p25α、烯酰辅酶A水合酶短链1、吡哆醇5′磷酸氧化酶、Mn超氧化物歧化酶、α烯醇化酶、抗氧化蛋白2、铁蛋白H链、谷氨酸脱氢酶、肽基脯氨酸顺反异构酶A、血清白蛋白前体、二氢嘧啶酶相关蛋白2。结论　上述差异蛋白有助于深入理解Tau蛋白病机制并有望在Tau蛋白病的早期诊断及新药开发上发挥作用。Objective To investigate the molecular mechanisms of tauopathies Comparative proteomic analysis of brain proteins was employed to study 4 patients with tauopathies ascompared with 4 controls Methods The brains of subjects who died without clinical or pathological involvement of nervous system and brains of patients with tauopathies were obtained at autopsy The brain proteins were run by immobilized pH gradient (IPG) isoelectric focusing electrophoresis as the first dimension, and then run by vertical SDS-PAGE as the second dimension The maps were visualized by silver staining or colloidal coomassie blue and analyzed with Image Master 2D Elite software The proteins of interest were in-gel digested and identified using MALDI-TOF mass spectrometry or MALDI-TOF/TOF tandem mass spectrometry Results 18 protein spots were differentially expressed as compared with age-matched nondemented control brains which were identified as glyceraldehyde 3-phosphate dehydrogenase, uracil DNA glycosylase, human superoxide dismutase, isocitrate dehydrogenase subunit, synaptotagmin I, thioredoxin peroxidase 1, glial fibrillary acidic protein, p25 alpha, enoyl coenzyme A hydratase short chain 1, pyridoxine-5′-phosphate oxidase, Mn-superoxide dismutase and alpha enolase, antioxidant protein 2, ferritin heavy chain, glutamate dehydrogenase precursor, peptidyl-prolyl cis-trans isomerase A, serum albumin precursor and dihydropyrimidinase-related protein 2 Conclusions We got a number of related-proteins of tauopathies Some proteins are quite useful for discovering the molecular mechanisms of tauopathies and may be helpful for diagnosis and of treatment tauopathies

关 键 词：Tau蛋白病 蛋白质组 电泳 凝胶 DNA糖苷 

分 类 号：R741[医药卫生—神经病学与精神病学]