Membrane Proteome Analysis of Cerulein-Stimulated Pancreatic Acinar Cells: Implication for Early Event of Acute Pancreatitis

Abstract

Background/Aims: Cerulein pancreatitis is similar to human edematous pancreatitis with dysregulation of the production and secretion of digestive enzymes, edema formation, cytoplasmic vacuolization and the death of acinar cells. We hypothesized that membrane proteins may be altered as the early event during the induction of acute pancreatitis. Present study aims to determine the differentially expressed proteins in the membranes of cerulein-treated pancreatic acinar cells. Methods: Pancreatic acinar AR42J cells were treated with 10 −8 M cerulein for 1 hour. Membrane proteins were isolated from the cells and separated by two-dimensional electrophoresis using pH gradients of 5-8. Membrane proteins were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the peptide digests. The differentially expressed proteins, whose expression levels were more or less than three-fold in cerulein-treated cells, were analyzed. Results: Two differentially expressed proteins (mannan-binding lectin-associated serine protease-2, heat shock protein 60) were up-regulated while four proteins (protein disulfide isomerase, γ-actin, isocitrate dehydrogenase 3, seven in absentia homolog 1A) were down-regulated by cerulein treatment in pancreatic acinar cells. These proteins are related to cell signaling, oxidative stress, and cytoskeleton arrangement. Conclusions: Oxidative stress may induce cerulein-induced cell injury and disturbances in defense mechanism in pancreatic acinar cells. (Gut Liver 2010; 4:84-93)

Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells

“…, 2012 ). Because γ-CYA is down-regulated in inflammatory conditions such as pancreatitis ( Lee et al. , 2010a ), it is tempting to speculate that decreased expression of γ-CYA can contribute to transdifferentiation of epithelial or other cell types into myofibroblasts in chronically inflamed tissues.…”

Role of Janus Kinase/Signal Transducers and Activators of Transcription in the Pathogenesis of Pancreatitis and Pancreatic Cancer

“…Pancreatic oxidative stress occurs during an early stage of pancreatitis 1-3. Scavenger therapy for reactive oxygen species (ROS) showed some success in experimental pancreatitis models, including cerulein pancreatitis 4,5.…”

“…Pancreatic oxidative stress occurs during an early stage of pancreatitis. 1 - 3 Scavenger therapy for reactive oxygen species (ROS) showed some success in experimental pancreatitis models, including cerulein pancreatitis. 4 , 5 In human acute pancreatitis, the increased levels of lipid peroxide in the bile or pancreatic tissue and subnormal levels of antioxidant vitamins in the blood were reported.…”

Rhein Protects Against Severe Acute Pancreatitis In vitro and In vivo by Regulating the JAK2/STAT3 Pathway

“…The SAP cell model was induced by cerulein. Pathological changes similar to those of human SAP were found during the induction ( Yu et al, 2008 ; Lee et al, 2010 ). Because cerulein is a CCK analogue, it binds to CCK receptors to activate signal transduction in pancreatic acinar cells.…”

“…According to published many literatures about rhein anti-inflammatory mechanism, such as the interactive relationships of rhein on multiple inflammatory signaling pathways and cellular processes ( Wang et al, 2020 ; Ding et al, 2020 ) The SAP cell model was induced by cerulein in AR42J cells, which pathological changes similar to those of human SAP were found during the induction ( Yu et al, 2008 ; Lee et al, 2010 ). AR42J cells were treated with 10 −8 mol/L of cerulein for 24 h. Then the model was tested by inflammatory cytokines and JAK2/STAT3 signalling pathway related proteins at 4 h. These alterations can be attributed to the action of cerulein.…”