Enzyme load in pancreatic acinar cells is increased in the early stages of acute pancreatitis induced by duct obstruction in rats

2000 ◽  
Vol 98 (2) ◽  
pp. 143 ◽  
Author(s):  
Aránzazu URUÑUELA ◽  
Manuel A. MANSO ◽  
Rosa Ma PINTO ◽  
Alberto ORFAO ◽  
Isabel DE DIOS
Keyword(s):  
Acute Pancreatitis ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Duct Obstruction ◽  
Early Stages ◽  
Enzyme Load

Enzyme load in pancreatic acinar cells is increased in the early stages of acute pancreatitis induced by duct obstruction in rats

2000 ◽  
Vol 98 (2) ◽  
pp. 143-150 ◽  
Author(s):  
Aránzazu URUÑUELA ◽  
Manuel A. MANSO ◽  
Rosa M PINTO ◽  
Alberto ORFAO ◽  
Isabel DE DIOS
Keyword(s):  
Acute Pancreatitis ◽  
Acinar Cells ◽  
Enzyme Synthesis ◽  
Pancreatic Acinar Cells ◽  
Intracellular Enzyme ◽  
Duct Obstruction ◽  
Early Stages ◽  
Morphological Studies ◽  
Pancreatic Duct Obstruction ◽  
Enzyme Load

Trypsinogen and amylase content has been analysed by flow cytometry in individual pancreatic cells from rats with acute pancreatitis induced by pancreatic duct obstruction, from the earliest stages to 48 h after obstruction. Parallel morphological studies of the pancreas by electron microscopy and analysis of various parameters for the diagnosis of pancreatitis will allow research into the possible relationship between intracellular enzyme load and the severity of pancreatitis. Progressive increases in amylase activity in ascites and plasma, the volume of ascites, haematocrit, vacuolization, oedema and macrophage infiltration were observed between 1.5 h and 12 h after duct obstruction. A progressive increase in enzyme content was also observed in individual acinar cells at this stage. Interestingly, the larger increase was for trypsinogen, so that the trypsinogen/amylase ratio was significantly increased in all acinar cells by 12 h after duct obstruction. This represents a risk factor for the development of pancreatitis. Sections of pancreas taken from rats that had duct obstruction for 48 h showed massive dilatation and disorganization of the endoplasmic reticulum, focal apoptosis and necrosis. These severe alterations would affect enzyme synthesis, as reflected by the significant decrease in the intracellular enzyme load observed at this stage. However, not all acinar cells were affected equally by the damage induced by pancreatitis: R1 cells appeared to be more sensitive than R2 cells. In conclusion, intracellular accumulation of digestive enzymes occurs at early stages of pancreatitis, and this effect is proportionally greater for trypsinogen, a finding that could explain the degree of severity achieved in the course of pancreatitis.

scholarly journals Absence of the neutrophil serine protease cathepsin G decreases neutrophil granulocyte infiltration but does not change the severity of acute pancreatitis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ali A. Aghdassi ◽  
Daniel S. John ◽  
Matthias Sendler ◽  
Christian Storck ◽  
Cindy van den Brandt ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Serine Protease ◽  
Acinar Cells ◽  
Neutrophil Infiltration ◽  
Cathepsin G ◽  
Pancreatic Acinar Cells ◽  
Neutrophil Granulocyte ◽  
Zymogen Activation ◽  
Trypsinogen Activation ◽  
Extracellular Matrix Components

AbstractAcute pancreatitis is characterized by an early intracellular protease activation and invasion of leukocytes into the pancreas. Cathepsins constitute a large group of lysosomal enzymes, that have been shown to modulate trypsinogen activation and neutrophil infiltration. Cathepsin G (CTSG) is a neutrophil serine protease of the chymotrypsin C family known to degrade extracellular matrix components and to have regulatory functions in inflammatory disorders. The aim of this study was to investigate the role of CTSG in pancreatitis. Isolated acinar cells were exposed to recombinant CTSG and supramaximal cholezystokinin stimulation. In CTSG−/− mice and corresponding controls acute experimental pancreatitis was induced by serial caerulein injections. Severity was assessed by histology, serum enzyme levels and zymogen activation. Neutrophil infiltration was quantified by chloro-acetate ersterase staining and myeloperoxidase measurement. CTSG was expessed in inflammatory cells but not in pancreatic acinar cells. CTSG had no effect on intra-acinar-cell trypsinogen activation. In CTSG−/− mice a transient decrease of neutrophil infiltration into the pancreas and lungs was found during acute pancreatitis while the disease severity remained largely unchanged. CTSG is involved in pancreatic neutrophil infiltration during pancreatitis, albeit to a lesser degree than the related neutrophil (PMN) elastase. Its absence therefore leaves pancreatitis severity essentially unaffected.

TRANSCRIPTION FACTOR PROFILING OF PANCREATIC ACINAR CELLS FOLLOWING TNF-α INDUCTION OF ACUTE PANCREATITIS.

Shock ◽  
2003 ◽  
Vol 19 (Supplement) ◽  
pp. 20
Author(s):  
L. Vona-Davis ◽  
K. Magabo ◽  
B. Jackson ◽  
T. Evans ◽  
D. Riggs ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Transcription Factor ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Tnf Α

Acinar Akt1 in pancreatic acinar cells supports proliferation and limits acinar-to-ductal metaplasia formation upon induction of acute pancreatitis

Pancreatology ◽  
2019 ◽  
Vol 19 ◽  
pp. S101
Author(s):  
Rong Chen ◽  
Ermanno Malagola ◽  
Maren Dietrich ◽  
Richard Zuellig ◽  
Marta Bombardo ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Acinar To Ductal Metaplasia

scholarly journals Inhibitors of ORAI1 Prevent Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models

2015 ◽  
Vol 149 (2) ◽  
pp. 481-492.e7 ◽  
Author(s):  
Li Wen ◽  
Svetlana Voronina ◽  
Muhammad A. Javed ◽  
Muhammad Awais ◽  
Peter Szatmary ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Mouse Models ◽  
Acinar Cells ◽  
Cytosolic Calcium ◽  
Pancreatic Acinar Cells ◽  
Associated Injury

scholarly journals CaMKII/proteasome/cytosolic calcium/cathepsin B axis was present in tryspin activation induced by nicardipine

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Juan Xiao ◽  
Houmin Lin ◽  
Binggang Liu ◽  
Junfei Jin
Keyword(s):  
Acute Pancreatitis ◽  
Calcium Channel ◽  
Cathepsin B ◽  
Acinar Cells ◽  
Proteasome Inhibition ◽  
Cytosolic Calcium ◽  
Pancreatic Acinar Cells ◽  
Prolonged Treatment ◽  
Early Event ◽  
Trypsinogen Activation

Abstract Premature trypsinogen activation is the early event of acute pancreatitis. Therefore, the studies on the processes of trypsinogen activation induced by compounds are important to understand mechanism underly acute pancreatitis under various conditions. Calcium overload in the early stage of acute pancreatitis was previously found to cause intracellular trypsinogen activation; however, treatment of acute pancreatitis using calcium channel blockers did not produced consistent results. Proteasome activity that could be inhibited by some calcium channel blocker has recently been reported to affect the development of acute pancreatitis; however, the associated mechanism were not fully understood. Here, the roles of nicardipine were investigated in trypsinogen activation in pancreatic acinar cells. The results showed that nicardipine could increase cathepsin B activity that caused trypsinogen activation, but higher concentration of nicardipine or prolonged treatment had an opposite effect. The effects of short time treatment of nicardipine at low concentration were studied here. Proteasome inhibition was observed under nicardipine treatment that contributed to the up-regulation in cytosolic calcium. Increased cytosolic calcium from ER induced by nicardipine resulted in the release and activation of cathepsin B. Meanwhile, calcium chelator inhibited cathepsin B as well as trypsinogen activation. Consistently, proteasome activator protected acinar cells from injury induced by nicardipine. Moreover, proteasome inhibition caused by nicardipine depended on CaMKII. In conclusion, CaMKII down-regulation/proteasome inhibition/cytosolic calcium up-regulation/cathepsin B activation/trypsinogen activation axis was present in pancreatic acinar cells injury under nicardipine treatment.

scholarly journals Free radicals and the pancreatic acinar cells: role in physiology and pathology

2005 ◽  
Vol 360 (1464) ◽  
pp. 2273-2284 ◽  
Author(s):  
M Chvanov ◽  
O.H Petersen ◽  
A Tepikin
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Acute Pancreatitis ◽  
Vascular Endothelium ◽  
Cell Injury ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Nitrogen Species ◽  
Key Enzyme ◽  
Oxide Synthase

Reactive oxygen and nitrogen species (ROS and RNS) play an important role in signal transduction and cell injury processes. Nitric oxide synthase (NOS)—the key enzyme producing nitric oxide (NO)—is found in neuronal structures, vascular endothelium and, possibly, in acinar and ductal epithelial cells in the pancreas. NO is known to regulate cell homeostasis, and its effects on the acinar cells are reviewed here. ROS are implicated in the early events within the acinar cells, leading to the development of acute pancreatitis. The available data on ROS/RNS involvement in the apoptotic and necrotic death of pancreatic acinar cells will be discussed.

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