帕金森病患者血清中M/Z2260肽的表达与鉴定  

Expression and Identification of a M/Z2260 Peptide in the Serum in Patients with Parkinson’s Disease

作　　者：叶懿文[1] 李尧华[1] 李爽[1] 李昕[1] 于顺[1] 杨慧[2] 陈彪[1] 

机构地区：[1]首都医科大学宣武医院老年病研究所神经生物学研究室教育部神经变性病重点实验室 [2]首都医科大学神经科学研究所

出　　处：《首都医科大学学报》2010年第6期748-751,共4页Journal of Capital Medical University

基　　金：国家高技术研究发展计划(863)项目(2006AA02A408);国家重点基础研究发展计划(973)(2011CB504101);国家自然科学基金(30271437; 30270482; 30430280; 81071014);北京市自然科学基金(7102067;7022011);北京市属高等学校人才强教计划资助项目(PHR200907113)~~

摘　　要：目的探讨帕金森病(Parkinson’s disease,PD)患者血清蛋白质生物标志物。方法选择原发性PD患者和正常人血清为样本,用弱阳离子交换(weak cationic exchange,WCX)磁珠捕获血清蛋白质组分,用基质辅助的激光解析离子化飞行时间质谱仪(matrix assisted laser desorption/ionization time of flight masss pectrometer,MALDI-TOF-MS)检测各捕获组分的蛋白质质谱,用统计学方法分析原发性PD患者和健康人的蛋白质谱,筛选差异分子,用LC-MALDI-TOF/TOF鉴定差异分子,用酶联免疫吸附法(ELISA)测定差异表达分子含量。结果在相对分子质量1000～50000范围内共检测到107个蛋白峰,其中9个蛋白质的表达发生显著变化(P<0.01)。一个相对分子质量为2260.1的蛋白质在PD血清中显著升高,是血清富组氨酸糖蛋白(histidine-rich glycoprotein,HRG)的C端降解产物。ELISA方法测定结果显示PD患者血清HRG含量低于正常人(P<0.05)。结论 PD患者血清低相对分子质量蛋白质的表达与正常人差异有统计学意义。HRG在PD患者血清中的含量低于正常人,而其C端降解片段在PD患者血清中的表达显著高于正常人。Objective To screen for the potential protein biomarkers in serum of patients with Parkinson’s disease.Methods The sera from patients with idiopathic PD and healthy blood donors were profiled by matrix assisted laser desorption/ionization time of flight mass spectrometer（MALDI-TOF-MS） combined with weak cationic exchange magnetic beads（WCX-MB）.The differential expression proteins were analyzed with statistical method.A M/Z2260.1 peptide was identified by LC-MALDI-TOF/TOF,and concentration of the intact protein containing M/Z2260.1 was determined by ELISA.Results Overall,107 protein peaks were detected in a mass range of 1 000～50 000.Of these,9 proteins were differentially expressed in the serum between PD patients and normals（P0.01）.A 2260.1u peptide was specifically expressed in serum in PD patients.It was sequenced as G.KFKSGFPQVSMFFTHTFPK,and was identified as a fragment deriving from C-terminal of histidine-rich glycoprotein（HRG）.ELISA show that the HRG concentration in serum in PD were significantly decreased（P0.05）.Conclusion Expression of the low molecular weight proteins in serum in PD was significantly different from the healthy controls.Although HRG concentration in serum in PD patients is lower than that of healthy controls,the M/Z2260.1 peptide,a C-terminal fragment of the HRG,is markedly increased in serum of PD patients.

关 键 词：帕金森病 富组氨酸糖蛋白 生物标志物 蛋白质组学 

分 类 号：R741.04[医药卫生—神经病学与精神病学]