Proteomic profiling in an animal model of acute pancreatitis

Abstract

Acute pancreatitis 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 acute pancreatitis 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 acute pancreatitis. 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 14-3-3proteins 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 acute pancreatitis.

Time-course proteomic analysis of taurocholate-induced necrotizing acute pancreatitis

“…In addition to native A1I3, strong bands corresponding to A1I3 fragments were detected. These fragments resulted from A1I3 anti-protease activity [5,7]. REG3A showed a different kinetics: no change was detected at 2 h post-induction, a moderate increase in protein expression was observed at 6 h, and a strong overexpression was visible at 18 h. In contrast, the concentration of cytochrome c in pancreatic extracts was shown to decrease progressively from T0 to T18h.…”

“…Results from those studies showed that proteomic analysis, while being obviously not comprehensive, allowed obtaining a general picture of the main proteins pathways involved in AP pathobiology. Mass spectrometry (MS) analysis also provided for some proteins, such as protease inhibitor alpha-1-inhibitor 3, precise sequence information that could be correlated with specific pathobiological processes [5,6]. Finally, investigation of the protective effect of thermal stress suggested that proteins associated to the acinar cell secretory pathway play an important role in the modulation of AP severity [7].…”

“…In previous studies, we used proteomic and peptidomic analyses to investigate the most widely used experimental model of AP in which disease is induced by parenteral injection of supramaximal doses of cerulein, a cholecystokinin analog [5][6][7]. This model is characterized by a relatively mild disease severity with pancreatic inflammation, apoptosis, mild necrosis and systemic inflammation [2].…”

Clusterin and Pycr1 alterations associate with strain and model differences in susceptibility to experimental pancreatitis

“…For example, Apoa1 is involved in inflammation and increased during pancreatitis in rats [23]; serpinA3k is reported to have a protective function in pancreatitis since it is a proteinase inhibitor and thus important to limit the activity of proteinases that are released prematurely in the pancreatic tissue [24]; and Prdx6 is associated with elevated oxidative stress [25,26]. None of these three proteins showed significant difference in protein levels between the two strains.…”

Effect of the Treatment with Alpha-Macroglobulin on the Development of Experimental Pancreatitis

“…The inhibitory eff ect of AM on proteinases suggests for it a protective role in the development of pancreatitis. The role of AM in the acute attack is undisputed and, once pancreatitis is established, its expression increases signifi cantly [ 20 ] . These fi ndings suggest a protective eff ect of MFP in the evolution of pancreatitis and that the increase of AM could be the limiting factor in the severity of acute pancreatitis.…”