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热休克诱导的急性胰腺炎保护作用的蛋白质组学分析。

Proteomic analysis of heat shock-induced protection in acute pancreatitis.

机构信息

Department of Bioinformatics and Structural Biology, Geneva Faculty of Medicine, Geneva, Switzerland.

出版信息

J Proteome Res. 2010 Nov 5;9(11):5929-42. doi: 10.1021/pr100695d. Epub 2010 Sep 23.

Abstract

Acute pancreatitis is an inflammatory disease of the pancreas, which can result in serious morbidity or death. Acute pancreatitis severity can be reduced in experimental models by preconditioning animals with a short hyperthermia prior to disease induction. Heat shock proteins 27 and 70 are key effectors of this protective effect. In this study, we performed a comparative proteomic analysis using a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and isobaric tagging to investigate changes in pancreatic proteins expression that were associated with thermal stress, both in healthy rats and in a model of caerulein-induced pancreatitis. In agreement with previous studies, we observed modulation of heat shock and inflammatory proteins expression in response to heat stress or pancreatitis induction. We also identified numerous other proteins, whose pancreatic level changed following pancreatitis induction, when acute pancreatitis severity was reduced by prior thermal stress, or in healthy rats in response to hyperthermia. Interestingly, we showed that the expression of various proteins associated with the secretory pathway was modified in the different experimental models, suggesting that modulation of this process is involved in the protective effect against pancreatic tissue damage.

摘要

急性胰腺炎是一种胰腺炎症性疾病,可导致严重的发病率或死亡率。在疾病诱导前对动物进行短暂的高热预处理,可以在实验模型中减轻急性胰腺炎的严重程度。热休克蛋白 27 和 70 是这种保护作用的关键效应物。在这项研究中,我们使用液相色谱-串联质谱 (LC-MS/MS) 分析和等压标记相结合的方法进行了比较蛋白质组学分析,以研究与热应激相关的胰腺蛋白表达变化,包括健康大鼠和蛙皮素诱导的胰腺炎模型。与先前的研究一致,我们观察到热应激或胰腺炎诱导时热休克和炎症蛋白表达的调节。我们还鉴定了许多其他蛋白质,这些蛋白质在急性胰腺炎严重程度通过预先的热应激减轻或在健康大鼠中对高热反应时,在胰腺炎诱导后其胰腺水平发生变化。有趣的是,我们表明与分泌途径相关的各种蛋白质的表达在不同的实验模型中发生了改变,提示该过程的调节参与了对胰腺组织损伤的保护作用。

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