同一家系ALS患者和正常人骨间肌组织的差异蛋白分析  

Differentially expressed proteins in interosseous muscle tissue between patients with familial amyotrophic lateral sclerosis and normal individuals in a family

作　　者：李玲[1,2] 马腾[1,2] 李佳潞 刘倩[1,2] 曹丽翠 黄银兰 LI Ling;MA Teng;LI Jialu(People’s Hospital of Ningxia Hui Autonomous Region,Ningxia 750001,China)

机构地区：[1]宁夏回族自治区人民医院,宁夏银川750001 [2]宁夏医科大学,宁夏银川750004 [3]宁夏银川市第一人民医院,宁夏银川750002

出　　处：《中风与神经疾病杂志》2025年第1期3-8,共6页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金资助项目(81260557)。

摘　　要：目的 应用同位素标记相对和绝对定量技术(iTRAQ),筛选同一家系肌萎缩侧索硬化症(FALS)患者与正常组骨间肌中相关蛋白的差异表达,确定该家系的致病蛋白,为治疗打下基础。方法 提取同一家系所有受试者骨间肌组织,运用iTRAQ技术,对所有蛋白质进行定性定量分析,获得患病组与正常组蛋白质表达谱,生物信息学分析筛选与FALS发病相关蛋白质,运用基因注释(GO)分析细胞成分,对蛋白进行分类分析。结果 经质谱鉴定共获得453种蛋白质,GO分析患病组与正常组共筛选出14种差异蛋白(P<0.05):与正常组相比有5种蛋白低表达(Ratio<1);有9种蛋白高表达(Ratio>1)。结论 TRIM 72、NADH脱氢酶[泛醌]1β亚基1、膜联蛋白A1、核心蛋白聚糖、谷胱甘肽过氧化物酶3、胶原蛋白α-1(Ⅻ)链、胶原蛋白α-2(Ⅰ)的链和胶原蛋白Ⅰ型-α1-亚型CRA-a,与FALS高度相关。26 S蛋白酶体调节亚基8、层粘连蛋白亚基α2、富亮氨酸重复蛋白、原纤维蛋白1、肌球蛋白8和皮连蛋白,可能与FALS相关。Objective To investigate the differential expression of related proteins in interosseous muscle tissue between patients with familial amyotrophic lateral sclerosis(FALS)and normal individuals in a family using the isobaric tags for relative and absolute quantitation(iTRAQ)technique,to identify the pathogenic proteins for this family,and to provide a basis for treatment.Methods Interosseous muscle tissue samples were collected from all subjects in this family,and the iTRAQ technique was used to perform qualitative and quantitative analyses for all proteins and obtain the expression profile of proteins in the disease group and the normal group.The bioinformatics methods were used to identify the proteins associated with the onset of FALS.A gene ontology(GO)analysis was performed for cell components,and a classification analysis was performed for related proteins.Results A total of 453 proteins were identified by mass spectrometry.The GO analysis obtained 14 differentially expressed proteins between the disease group and the normal group(P<0.05),and compared with the normal group,the disease group had the low expression of 5 proteins(Ratio<1)and the high expression of 9 proteins(Ratio>1).Conclusion This study identifies 8 proteins that are highly associated with FALS,i.e.,tripartite motif-containing protein 72,NADH dehydrogenase[ubiquinone]1 beta subcomplex subunit 1,annexin A1,decorin,glutathione peroxidase 3,collagen alpha-1(Ⅻ)chain,collagen alpha-2(Ⅰ)chain,and collagen type I alpha 1 isoform CRA-a.There are 6 proteins that might be associated with FALS,i.e.,26 S protease regulatory subunit 8,laminin subunit alpha-2,prolargin,fibrillin-1,myosin-8,and dermatopontin.

关 键 词：肌萎缩侧索硬化症 蛋白质组学 同位素标记相对和绝对定量技术 

分 类 号：R744.8[医药卫生—神经病学与精神病学]