脑老化糖基化终末产物上调BACE1活性促进Aβ生成  

Advanced glycation end products （AGEs） increase Aβ generation though up--regulated BACE1 activity in APPsw--N2a cells

作　　者：孔繁军[1,2] 王威[2] 于璐[2] 赵磊[2] 冀拓[2] 朴丽颖[2] 任天云[2] 崔德华[2] 

机构地区：[1]国家康复辅具研究中心附属康复医院,100176 [2]北京大学医学部教育部和卫生部神经科学重点实验室

出　　处：《神经疾病与精神卫生》2013年第2期125-127,共3页Journal of Neuroscience and Mental Health

基　　金：国家自然科学基金资助项目（30973145,81171015）;科技部项目（2012CB911004）;国家基础科学人才培养基金及北医创新人才基金

摘　　要：目的探讨糖基化终末产物（AGEs）在β-淀粉样蛋白（Ap）产生中分子机制。方法以APPsw—N2a细胞为AD细胞模型，将细胞随机分为3组，空白对照组、AGEs组、AGEs＋抗RAG抗体组。采用ELIsA方法检测各组Aβ40和Aβ42的表达水平，并用荧光检测法检测BACE1的活性。结果与对照组相比，AGEs组AD40、Aβ42表达水平及BACE1活性明显增加，差异有统计学意义（P〈0．01）；预先用抗RAG中和抗体（1：100）1h后，A840，Aβ2表达水平及BACE1活性与AGEs组相比较明显减少，差异有统计学意义（P〈O．05）。结论AGEs可能通过上调BACEl的活性促使APPsw—N2a细胞A8生成增加，提示AGEs可能在AD发生、发展中起重要作用。Objective To investigate molecular mechanism of advanced glycation end products （AGEs） in the generation of β-amyloid protein（Aβ）. Methods The APPsw--N2a cells were divided into three groups randomly（the control group, the AGEs graup, the AGEs＋RAG group）. To examine the ceils＇ growth state with MTT metabolic rate and determine the best concentration and time of the AGEs, and to observe the generation of Aβ by ELISA. Results Our data showed that APP was up-- reg-ulated by AGEs in vitro, and pretreatment of cells with an anti--RAG--antibody blocked the effects of AGEs. In conditioned medium, the level of Aβ increased after AGE treatment. Conclusions AGEs could promote the generation of Aβ by up--regulating the activities of BACE.

关 键 词：阿尔茨海默病 糖基化终末产物 Β-淀粉样蛋白 

分 类 号：R587.2[医药卫生—内分泌]