神经节苷脂促进β-淀粉样蛋白生成及其二者协同分布  

Effect of Ganglioside GM1 on the Production of Amyloid β-protein and Their Co-Localization

作　　者：王雪[1] 何其华[2] 阮燕[1] 张岱[1] 

机构地区：[1]北京大学精神卫生研究所,100083 [2]北京大学基础医学院,100083

出　　处：《中国心理卫生杂志》2003年第2期89-93,共5页Chinese Mental Health Journal

基　　金：国家自然科学基金 (39870 2 76 ;39840 0 1 0 );国家重点基础研究发展规划项目(G1 9990 640 0 7)资助

摘　　要：目的 :探讨神经节苷脂GM1干扰 β -淀粉样蛋白前体 (APP)正常代谢途径以及增加 β -淀粉样蛋白 (Aβ)生成的可能机制 ,以确立GM1在阿尔茨海默病 (AD)脑淀粉样变性过程中的特定作用。 方法 :选用人类 β -淀粉样蛋白前体基因 (APP6 95)转染细胞模型 ,用IP -Western印迹法观察GM1,对细胞APP代谢产物Aβ释放的影响 ;应用激光共聚焦扫描显微术 (LSCM )分别定量分析不同浓度GM1作用下细胞内Aβ40和Aβ42荧光强度的变化 ;通过双重免疫荧光标记确定GM1与Aβ4 0 和 /或Aβ4 2 的协同定位分布。结果 :GM1干扰细胞APP水解代谢和促进Aβ的释放 ;细胞内Aβ4 0 和Aβ4 2 荧光强度均随GM1浓度的增加而增强 ;内、外源性GM1分别与Aβ4 0 和Aβ4 2 在细胞内协同定位。结论 :提示GM1通过与Aβ的协同分布 。Objective: This work will further investigate the mechanism of the disruption of ganglioside GM1 on the metabolism of amyloid protein precursor(APP) and the production of amyloid β-protein(Aβ), to establish the special function in the pathogenesis of Alzheimer's Disease(AD) Method: This work used the model of human neuroblastoma cells transfected human APP cDNA to analyze the effect of the various concentration of GM1 on the level of extracellular Aβ by IP-Western Blot, and the level of intracellular Aβ by Cofocal; to analyze colocalization of GM1 with Aβ 40 / Aβ 42 by double immunoflurescence labeling Results: This study have revealed that GM1 could promote the generation of Aβ; the immunlfluorecence density of intracellular Aβ 40 /Aβ 42 is correlated to the concentration of GM1 in the dose-dependent fashion; It demonstrates that GM1 is overlapped with Aβ 40 / Aβ 42 by double immunofluorescence staining Concluslon: This study points out that the colocalization of GM1 with intracellular Aβ has directly involved in the amyloidogenesis of Alzheimer's Disease

关 键 词：神经节苷脂 β—淀粉样蛋白生成 阿尔获海默病 协同分布 

分 类 号：R749.16[医药卫生—神经病学与精神病学]