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急性胰腺炎动物模型中的蛋白质组学分析

Proteomic profiling in an animal model of acute pancreatitis.

作者信息

Fétaud Vanessa, Frossard Jean-Louis, Farina Annarita, Pastor Catherine M, Bühler Léo, Dumonceau Jean-Marc, Hadengue Antoine, Hochstrasser Denis F, Lescuyer Pierre

机构信息

Biomedical Proteomics Research Group, Department of Bioinformatics and Structural Biology, Geneva Faculty of Medicine, Geneva, Switzerland.

出版信息

Proteomics. 2008 Sep;8(17):3621-31. doi: 10.1002/pmic.200800066.

Abstract

Acute pancreatitis (AP) is an inflammatory disease of the pancreas, which evolves in approximately 20% of the patients to a severe illness associated with a high mortality rate. In this study, we performed a comparative proteomic analysis of pancreatic tissue extracts from rats with AP and healthy rodent controls in order to identify changes in protein expression related to the pathobiological processes of this disease. Pancreatic extracts from diseased and controls rats were analyzed by 2-DE and MS/MS. A total of 125 proteins were identified from both samples. Comparative analysis allowed the detection of 42 proteins or protein fragments differentially expressed between diseased and control pancreas, some of them being newly described in AP. Interestingly, these changes were representative of the main pathobiological pathways involved in this disease. We observed activation of digestive proteases and increased expression of various inflammatory markers, including several members of the alpha-macroglobulin family. We also detected changes related to oxidative and cell stress responses. Finally, we highlighted modifications of 14-3-3 proteins that could be related to apoptosis regulation. These results showed the interest of proteomic analysis to identify changes characterizing pancreatic tissue damage and, therefore, to highlight new potential biomarkers of AP.

摘要

急性胰腺炎(AP)是胰腺的一种炎症性疾病,约20%的患者会发展为重症疾病,死亡率很高。在本研究中,我们对患有AP的大鼠和健康啮齿动物对照的胰腺组织提取物进行了比较蛋白质组学分析,以确定与该疾病病理生物学过程相关的蛋白质表达变化。通过二维电泳(2-DE)和串联质谱(MS/MS)分析患病大鼠和对照大鼠的胰腺提取物。从两个样本中共鉴定出125种蛋白质。比较分析发现,患病胰腺和对照胰腺之间有42种蛋白质或蛋白质片段表达存在差异,其中一些是AP中首次描述的。有趣的是,这些变化代表了该疾病涉及的主要病理生物学途径。我们观察到消化蛋白酶的激活以及多种炎症标志物的表达增加,包括α-巨球蛋白家族的几个成员。我们还检测到与氧化和细胞应激反应相关的变化。最后,我们强调了14-3-3蛋白的修饰可能与细胞凋亡调节有关。这些结果表明蛋白质组学分析有助于识别胰腺组织损伤的特征性变化,从而突出AP新的潜在生物标志物。

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