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模拟微重力暴露过程中内皮细胞分泌的蛋白质的修饰。

Modification of proteins secreted by endothelial cells during modeled low gravity exposure.

机构信息

Department of Experimental Biology, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.

出版信息

J Cell Biochem. 2011 Jan;112(1):265-72. doi: 10.1002/jcb.22921.

Abstract

The exposure of the human body to microgravity, conditions that occurs during space flights, causes significant changes in the cardiovascular system. Many cell types have been involved in these changes, and the endothelium seems to play a major role. In endothelial cells (EC), it has been shown that modeled low gravity impairs nitric oxide synthesis, cell adhesion, extracellular matrix composition, cytoskeleton organization, cytokines, and growth factors secretion. Nevertheless, detailed analysis of EC physiological changes induced by microgravity exposure is still lacking. Secretome analysis is one of the most promising approaches for the identification of biomarkers directly related to the physiopathological cellular state. In this study, we analyzed in details the modifications of EC secretome by using umbilical vein endothelial (HUVE) cells exposed to modeled low gravity conditions. By adopting a two-dimensional (2-D) proteomic approach, in conjunction with a technique for the compression of the dynamic range of proteins, we observed that modeled low gravity exposure of HUVE cells affected the secretion of proteins involved in the regulation of cytoskeleton assembly. Moreover, by using Luminex® suspension array systems, we found that the low gravity condition decreased in ECs the secretion of some key pro-inflammatory cytokines, including IL-1α and IL-8, and of the pro-angiogenic factor bFGF. On the contrary, microgravity increase the secretion of two chemokines (Rantes and Eotaxin), involved in leukocytes recruitment.

摘要

人体暴露在微重力环境下,这种情况发生在太空飞行中,会导致心血管系统发生重大变化。许多细胞类型都参与了这些变化,而内皮细胞似乎起着主要作用。在内皮细胞(EC)中,已经表明模拟的低重力会损害一氧化氮合成、细胞黏附、细胞外基质组成、细胞骨架组织、细胞因子和生长因子的分泌。然而,对微重力暴露引起的 EC 生理变化的详细分析仍然缺乏。分泌组分析是鉴定与细胞生理状态直接相关的生物标志物的最有前途的方法之一。在这项研究中,我们使用暴露于模拟低重力条件下的脐静脉内皮(HUVE)细胞,详细分析了 EC 分泌组的变化。通过采用二维(2-D)蛋白质组学方法,结合一种压缩蛋白质动态范围的技术,我们观察到 HUVE 细胞暴露于模拟低重力环境会影响参与细胞骨架组装调节的蛋白质的分泌。此外,通过使用 Luminex®悬浮阵列系统,我们发现低重力条件会降低内皮细胞中一些关键促炎细胞因子(包括 IL-1α 和 IL-8)和促血管生成因子 bFGF 的分泌。相反,微重力会增加两种趋化因子(Rantes 和 Eotaxin)的分泌,这两种趋化因子参与白细胞募集。

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