Secretion of long Aβ-related peptides processed at ε-cleavage site is dependent on the α-secretase pre-cutting
Secretion of long Aβ-related peptides processed at ε-cleavage site is dependent on the α-secretase pre-cutting
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DOI：
10.1016/j.febslet.2004.06.034
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发表时间：
2004-07-16
期刊：
影响因子：
3.5
通讯作者：
Kametani, F
中科院分区：
文献类型：
--
作者：
Kametani, F
AV是阿尔茨海默氏病中脑中淀粉样蛋白的主要组分，并且通过涉及α-、β-和γ-分泌酶的连续蛋白水解裂解衍生自阿尔茨海默氏淀粉样蛋白前体蛋白（APP）。最近，γ-分泌酶被证明在APP的细胞质膜边界附近切割（称为ε-切割），以及在膜结构域的中间切割（γ-切割）。然而，γ-和ε-裂解之间的精确关系仍然未知。本文采用免疫沉淀和液相色谱-离子阱质谱法对COS-1细胞培养液和人脑提取液中的Abeta相关肽进行了分析，发现了一些Abeta相关的长肽，起始于16 Lys-23 Asp，终止于43 Thr-52 Leu。这些结果表明，在ε-切割位点切割的较长的A β-相关肽在正常条件下分泌，并且依赖于α-分泌酶切割产物。(C)2004年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
AV is the major component of amyloid in the brain in Alzheimer's disease and is derived from Alzheimer amyloid precursor protein (APP) by sequential proteoiytic cleavage involving alpha-, beta- and gamma-secretase. Recently, gamma-secretase was shown to cleave near the cytoplasmic membrane boundary of APP (called the epsilon-cleavage), as well as in the middle of the membrane domain (gamma-cleavage). However, the precise relationship between gamma- and epsilon-cleavage is still unknown. In this paper, I analyzed Abeta-related peptides using immunoprecipitation and liquid chromatography ion trap mass spectrometer and found some long Abeta-related peptides, starting at Abeta residues 16Lys-23Asp and ending at 43Thr-52Leu, in the culture media of COS-1 cells and in human brain extract. These results indicated that longer Abeta-related peptides cleaved at epsilon-cleavage site were secreted under normal conditions and were dependent on the alpha-secretase cleavage products. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.