Murine synaptosomal lipid raft protein and lipid composition are altered by expression of human apoE 3 and 4 and by increasing age
Murine synaptosomal lipid raft protein and lipid composition are altered by expression of human apoE 3 and 4 and by increasing age
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DOI：
10.1016/j.jns.2004.11.037
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发表时间：
2005-03-15
影响因子：
4.4
通讯作者：
Yanagisawa, K
中科院分区：
文献类型：
--
作者：
Igbavboa, U;Eckert, GP;Yanagisawa, K
载脂蛋白E(ApoE)4和衰老是阿尔茨海默病(AD)的危险因素。表达人载脂蛋白E4的小鼠和老年野生型小鼠在突触质膜中的胆固醇跨双层分布相似，但与载脂蛋白E3小鼠和年轻小鼠相比有显着差异。观察到胆固醇分布的最大变化是在SPM外表面传单中，那里的胆固醇增加了一倍。脂筏被认为与面外小叶相关，我们提出脂筏蛋白和脂组成可能与apoE基因和年龄有关。从不同年龄组(2、12、24月龄)表达人apoE3和apoE4的小鼠的突触体内分离出脂筏。检测脂筏标记物、碱性磷酸酶(ALP)、Flotillin-1、胆固醇和鞘磷脂(SM)。与年轻apoE3小鼠相比，年轻apoE4小鼠的脂筏在碱性磷酸酶活性和fltillin-1丰度方面与老年小鼠更相似。在年轻的apoE3和apoE4小鼠中，脂筏胆固醇和鞘磷脂水平没有显着差异，但两种基因型的脂筏胆固醇水平都随着年龄的增长而增加。本研究的结果表明，阿尔茨海默病的两个危险因素apoE4基因和年龄增加对脑脂筏蛋白标记物的影响相似，这些发现支持胆固醇跨双层分布与脂筏功能有关的观点。(C)2004爱思唯尔B.V.保留所有权利。
Apolipoprotein E (apoE) 4 and aging are risk factors for Alzheimer's disease (AD). Mice expressing human apoE4 and aged wild-type mice show a similarity in the transbilayer distribution of cholesterol in synaptic plasma membranes (SPMs) but differ markedly compared with apoE3 mice and young mice. The largest changes in cholesterol distribution were observed in the SPM exofacial leaflet where there was a doubling of cholesterol. Lipid rafts are thought to be associated with the exofacial leaflet, and we proposed that lipid raft protein and lipid composition would be associated with apoE genotype and age. Lipid rafts were isolated from synaptosomes of different age groups (2, 12, 24 months) of mice expressing human apoE3 and apoE4. Lipid raft markers, alkaline phosphatase (ALP), flotillin-1, cholesterol and sphingomyelin (SM) were examined. Lipid rafts of young apoE4 mice were more similar to older mice as compared with young apoE3 mice in reductions in alkaline phosphatase activity and flotillin-1 abundance. Lipid raft cholesterol and sphingomyelin levels were not significantly different between the young apoE3 and apoE4 mice but cholesterol levels of lipid rafts did increase with age in both genotypes. Results of the present study demonstrate that the two risk factors for Alzheimer's disease, apoE4 genotype and increasing age have similar effects on brain lipid raft protein markers and these findings support the notion that the transbilayer distribution of cholesterol is associated with lipid raft function. (c) 2004 Elsevier B.V. All rights reserved.