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人类分泌蛋白质组图谱计划:对健康与疾病状况的影响

The human secretome atlas initiative: implications in health and disease conditions.

作者信息

Brown Kristy J, Seol Haeri, Pillai Dinesh K, Sankoorikal Binu-John, Formolo Catherine A, Mac Jenny, Edwards Nathan J, Rose Mary C, Hathout Yetrib

机构信息

Center for Genetic Medicine Research, Children's National Medical Center, Washington DC 20010, USA.

出版信息

Biochim Biophys Acta. 2013 Nov;1834(11):2454-61. doi: 10.1016/j.bbapap.2013.04.007. Epub 2013 Apr 19.

Abstract

Proteomic analysis of human body fluids is highly challenging, therefore many researchers are redirecting efforts toward secretome profiling. The goal is to define potential biomarkers and therapeutic targets in the secretome that can be traced back in accessible human body fluids. However, currently there is a lack of secretome profiles of normal human primary cells making it difficult to assess the biological meaning of current findings. In this study we sought to establish secretome profiles of human primary cells obtained from healthy donors with the goal of building a human secretome atlas. Such an atlas can be used as a reference for discovery of potential disease associated biomarkers and eventually novel therapeutic targets. As a preliminary study, secretome profiles were established for six different types of human primary cell cultures and checked for overlaps with the three major human body fluids including plasma, cerebrospinal fluid and urine. About 67% of the 1054 identified proteins in the secretome of these primary cells occurred in at least one body fluid. Furthermore, comparison of the secretome profiles of two human glioblastoma cell lines to this new human secretome atlas enabled unambiguous identification of potential brain tumor biomarkers. These biomarkers can be easily monitored in different body fluids using stable isotope labeled standard proteins. The long term goal of this study is to establish a comprehensive online human secretome atlas for future use as a reference for any disease related secretome study. This article is part of a Special Issue entitled: An Updated Secretome.

摘要

对人体体液进行蛋白质组学分析极具挑战性,因此许多研究人员正将精力转向分泌蛋白质组分析。目的是在分泌蛋白质组中确定潜在的生物标志物和治疗靶点,这些标志物和靶点可在易于获取的人体体液中找到踪迹。然而,目前缺乏正常人类原代细胞的分泌蛋白质组图谱,这使得评估当前研究结果的生物学意义变得困难。在本研究中,我们试图建立从健康供体获取的人类原代细胞的分泌蛋白质组图谱,目标是构建一个人类分泌蛋白质组图谱集。这样的图谱集可作为发现潜在疾病相关生物标志物以及最终发现新型治疗靶点的参考。作为一项初步研究,我们建立了六种不同类型人类原代细胞培养物的分泌蛋白质组图谱,并检查了它们与三种主要人体体液(血浆、脑脊液和尿液)的重叠情况。这些原代细胞分泌蛋白质组中鉴定出的1054种蛋白质中,约67%至少在一种体液中出现。此外,将两个人类胶质母细胞瘤细胞系的分泌蛋白质组图谱与这个新的人类分泌蛋白质组图谱集进行比较,能够明确鉴定出潜在的脑肿瘤生物标志物。使用稳定同位素标记的标准蛋白质可在不同体液中轻松监测这些生物标志物。本研究的长期目标是建立一个全面的在线人类分泌蛋白质组图谱集,以供未来用于任何与疾病相关的分泌蛋白质组研究参考。本文是名为:更新后的分泌蛋白质组的特刊的一部分。

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