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Diagnostic value of peptidome analyses for protease activated pathological conditions beyond cancer diagnosis

肽组分析对癌症诊断之外的蛋白酶激活病理状况的诊断价值

基本信息

批准号：
19390156
负责人：
HASHIGUCHI Teruto
金额：
$ 12.4万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2007
资助国家：
日本
起止时间：
2007 至 2009
项目状态：
已结题

项目摘要

Human serum contains thousands of proteolytically derived low-molecular-weight peptide fragments (serum peptidome). The concept of utilizing the serum peptidome for cancer diagnosis has been developed. A pathological serum peptidome appears when the homeostatic balance between proteases and protease inhibitors is disrupted. We hypothesize if analyses of the serum peptidome are of diagnostic value as information on which molecules are disrupted, and the pathological course it will take in unknown pathological conditions and disseminated intravascular coagulation (DIC). We analyzed the serum peptidome in 3 stages (early stage, pre-DIC and DIC stages) in one patient with POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes) syndrome, an intractable disease with unknown pathology, using a 1-dimensional gel electrophoresis/ matrix-assisted laser desorption/ionization-mass spectrometry (1-DE/MS)-based rapid quantitative approach. A very large number of peptide fragments appeared in the DIC stage, compared to pre-DIC. In addition, we identified fragments of transthyretin (ALGISPFHEHAEVVFTANDSGPR, m/z 2,451.18) and α1-antitrypsin (EDPQGDAAQKTDTSHHDQDHPTFN, m/z 2,691.02) that significantly increased in the DIC stage, compared to those in the pre-DIC stage. Rapid analyses of the serum peptidome may lead to a diagnostic method that can predict on-going protease activated pathological conditions and help to decide on multilateral strategies including nutritional support and drug therapy.

人血清含有数千个蛋白水解衍生的低分子量肽片段（血清肽组）。利用血清肽组进行癌症诊断的概念已经被提出。当蛋白酶和蛋白酶抑制剂之间的稳态平衡被破坏时，就会出现病理性血清肽组。我们假设血清肽组的分析是否具有诊断价值，因为它可以提供有关哪些分子被破坏的信息，以及在未知病理条件和弥散性血管内凝血（DIC）中它将采取的病理过程。我们使用一维凝胶电泳/基质辅助激光解吸/电离质谱分析了 1 例 POEMS（多发性神经病、器官肿大、内分泌病、M 蛋白和皮肤变化）综合征患者的 3 个阶段（早期、DIC 前期和 DIC 阶段）的血清肽组，POEMS 是一种病理未知的难治性疾病。基于 (1-DE/MS) 的快速定量方法。与 DIC 前相比，DIC 阶段出现了大量的肽片段。此外，我们还发现转甲状腺素蛋白 (ALGISPFHEHAEVVFTANDSGPR，m/z 2,451.18) 和 α1-抗胰蛋白酶 (EDPQGDAAQKTDTSHHDQDHPTFN，m/z 2,691.02) 的片段在 DIC 阶段与 DIC 前阶段相比显着增加。对血清肽组的快速分析可能会产生一种诊断方法，可以预测正在进行的蛋白酶激活的病理状况，并有助于决定包括营养支持和药物治疗在内的多边策略。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The diagnostic value of endothelial function as a potential sensor of fatigue in health.

DOI：
10.2147/vhrm.s8950
发表时间：
2010-03-24
期刊：
Vascular health and risk management
影响因子：
2.9
作者：
Ohno Y;Hashiguchi T;Maenosono R;Yamashita H;Taira Y;Minowa K;Yamashita Y;Kato Y;Kawahara K;Maruyama I
通讯作者：
Maruyama I

Serum VEGF increases in diabetic polyneuropathy, particularly in the neurologically active symptomatic stage