Amyloid precursor protein mediates monocyte adhesion in AD tissue and apoE(-)/(-) mice.
Amyloid precursor protein mediates monocyte adhesion in AD tissue and apoE(-)/(-) mice.
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DOI：
10.1016/j.neurobiolaging.2008.10.013
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发表时间：
2010-11
影响因子：
4.2
通讯作者：
Combs, Colin K.
中科院分区：
文献类型：
--
作者：
Austin, Susan A.;Combs, Colin K.
淀粉样前体蛋白（APP）是一种高度保守且广泛表达的1型膜整合蛋白。大量数据表明它在细胞粘附中起作用。例如，APP结合细胞外基质的组分以传播细胞内信号传导应答。为了研究炎症血管中与粘连相关的变化，研究人员检查了载脂蛋白E −/−（apoE−/−）小鼠的大脑与APP相关的变化，然后将其与人类阿尔茨海默病（AD）大脑进行比较。来自小鼠apoE−/−和人类AD脑的脑血管显示APP、在酪氨酸残基682处磷酸化的APP（pAPP）和Aβ的强免疫反应性。此外，对小鼠apoE−/−和AD脑的蛋白质印迹分析显示，APP、pAPP的蛋白质水平在统计学上更高，APP与酪氨酸激酶Src的相关性增加。最后，利用改良的Stamper-Woodruff粘附试验，我们证明单核细胞与apoE−/−和AD脑内皮细胞的粘附部分依赖于APP。这些数据表明，内皮APP功能加上Aβ产生增加参与了与动脉粥样硬化和AD相关的血管功能障碍。
Amyloid precursor protein (APP) is a type 1 integral membrane protein which is highly conserved and ubiquitously expressed. Numerous data suggest it functions in cellular adhesion. For example, APP binds components of the extracellular matrix to propagate intracellular signaling responses. In order to investigate adhesion-related changes in inflamed vasculature, brains from apolipoprotein E −/− (apoE−/−) mice were examined for changes related to APP then compared to human Alzheimer’s disease (AD) brains. Cerebrovasculature from mouse apoE−/− and human AD brains revealed strong immunoreactivity for APP, APP phosphorylated at tyrosine residue 682 (pAPP) and Aβ. Further, Western blot analyses from mouse apoE−/− and AD brains showed statistically higher protein levels of APP, pAPP and increased APP association with the tyrosine kinase, Src. Lastly, utilizing a modified Stamper-Woodruff adhesion assay, we demonstrated that adhesion of monocytic cells to apoE−/− and AD brain endothelium is partially APP-dependent. These data suggest that endothelial APP function coupled with increased Aβ production are involved in the vascular dysfunction associated with atherosclerosis and AD.
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