Ciallella J R, Rangnekar V V, McGillis J P
Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington.
J Neurosci Res. 1994 Apr 15;37(6):769-76. doi: 10.1002/jnr.490370611.
One of the pathological lesions in Alzheimer's disease (AD) is the amyloid or senile plaque. The plaque core is predominantly made up of amyloid beta peptide (A beta), a 42-43 amino acid peptide derived from amyloid precursor protein (APP). APP is a membrane bound glycoprotein which is expressed ubiquitously in many cells. Although normal or pathological functions for APP are not well understood, several observations suggest that APP may play a role in cellular stress and inflammation at the endothelial cell/vascular barrier. APP is found in platelets and endothelial cells, it can inhibit a blood coagulation factor, and secreted APP can be neuroprotective. Changes in expression of APP during cellular stress or inflammation may contribute to pathological deposition of A beta. In the present studies, expression of APP in human endothelial cells was examined following heat shock. In human umbilical vein endothelial cells (HUVECs) exposed to 42 degrees C for 30 min, there was a five- to eight-fold increase in APP mRNA levels which peaked at 4 hr. The increase in APP mRNA was followed by an increase in APP protein immunoreactivity in the cytoplasm in a perinuclear Golgi-like region, and in discrete granular cytoplasmic structures. Immunoblot analysis of APP in the cell media found a transient increase in APP which peaked at 1 hr after heat shock. These results suggest that cellular stress induces the secretion of APP from endothelial cells followed by a subsequent increase in APP mRNA and protein synthesis. The upregulation of APP mRNA and protein supports a cellular stress role for APP.
阿尔茨海默病（AD）的病理病变之一是淀粉样蛋白或老年斑。斑块核心主要由淀粉样β肽（Aβ）组成，Aβ是一种由淀粉样前体蛋白（APP）衍生而来的含42 - 43个氨基酸的肽。APP是一种膜结合糖蛋白，在许多细胞中普遍表达。尽管APP的正常或病理功能尚未完全明确，但一些观察结果表明，APP可能在内皮细胞/血管屏障的细胞应激和炎症中发挥作用。APP存在于血小板和内皮细胞中，它可以抑制一种凝血因子，并且分泌型APP具有神经保护作用。细胞应激或炎症期间APP表达的变化可能导致Aβ的病理沉积。在本研究中，热休克后检测了人内皮细胞中APP的表达。在暴露于42℃30分钟的人脐静脉内皮细胞（HUVECs）中，APP mRNA水平增加了5至8倍，在4小时达到峰值。APP mRNA增加后，在核周高尔基体样区域的细胞质以及离散的颗粒状细胞质结构中，APP蛋白免疫反应性增加。对细胞培养基中APP的免疫印迹分析发现，热休克后1小时APP出现短暂增加，峰值出现在该时刻。这些结果表明，细胞应激诱导内皮细胞分泌APP，随后APP mRNA和蛋白质合成增加。APP mRNA和蛋白质的上调支持了APP在细胞应激中的作用。
