Kitazume Shinobu, Yoshihisa Akiomi, Yamaki Takayoshi, Oikawa Masayoshi, Tachida Yuriko, Ogawa Kazuko, Imamaki Rie, Takeishi Yasuchika, Yamamoto Naomasa, Taniguchi Naoyuki
Disease Glycomics Team, RIKEN-Max Planck Joint Research Center, Global Research Cluster, RIKEN, Wako, Saitama, Japan.
Department of Advanced Cardiac Therapeutics, Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan.
Proteomics Clin Appl. 2013 Oct;7(9-10):657-63. doi: 10.1002/prca.201200135. Epub 2013 Sep 9.
Most Alzheimer disease patients show deposition of amyloid β (Aβ) peptide in blood vessels as well as the brain parenchyma. We previously found that vascular endothelial cells express amyloid β precursor protein (APP) 770, a different APP isoform from neuronal APP695, and that they produce amyloid β peptide. We analyzed the glycosylation of APP770 and found that O-glycosylated sAPP770 is preferentially processed by proteases for Aβ production. Because the soluble APP cleavage product sAPP is considered to be a possible marker for Alzheimer disease diagnosis, sAPP, consisting of a mixture of these variants, has been widely measured. We hypothesized that measurement of the endothelial APP770 cleavage product in patients separately from that of neuronal APP695 would enable us to discriminate between endothelial and neurological dysfunctions. Our recent findings, showing that the level of plasma sAPP770 is significantly higher in patients with acute coronary syndrome, raise the possibility that sAPP770 could be an indicator of endothelial dysfunction. In this review, we first describe the expression, glycosylation, and processing of APP770, and then discuss sAPP770 as a novel biomarker candidate of acute coronary syndrome.
大多数阿尔茨海默病患者的血管以及脑实质中都有β淀粉样蛋白(Aβ)肽沉积。我们之前发现血管内皮细胞表达淀粉样前体蛋白(APP)770,这是一种与神经元APP695不同的APP异构体,并且它们会产生β淀粉样蛋白肽。我们分析了APP770的糖基化情况,发现O-糖基化的可溶性APP770(sAPP770)优先被蛋白酶加工以产生Aβ。由于可溶性APP裂解产物sAPP被认为是阿尔茨海默病诊断的一个可能标志物,由这些变体混合物组成的sAPP已被广泛检测。我们推测,将患者体内内皮细胞APP770的裂解产物与神经元APP695的裂解产物分开测量,将使我们能够区分内皮功能障碍和神经功能障碍。我们最近的研究结果表明,急性冠状动脉综合征患者血浆sAPP770水平显著升高,这增加了sAPP770可能是内皮功能障碍指标的可能性。在这篇综述中,我们首先描述APP770的表达、糖基化和加工过程,然后讨论sAPP770作为急性冠状动脉综合征新型生物标志物候选物的情况。