scholarly journals The role of Ca2+ influx in endocytic vacuole formation in pancreatic acinar cells

2015 ◽  
Vol 465 (3) ◽  
pp. 405-412 ◽  
Author(s):  
Svetlana Voronina ◽  
David Collier ◽  
Michael Chvanov ◽  
Ben Middlehurst ◽  
Alison J. Beckett ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Vacuole Formation

Endocytic vacuoles are ‘initiating’ organelles in the development of acute pancreatitis. In the present study, we identified the important roles of store-operated Ca2+ influx and Ca2+-dependent proteases (calpains) in the formation of these organelles.

Pancreatic gene expression during the initiation of acute pancreatitis: identification of EGR-1 as a key regulator

2003 ◽  
Vol 14 (1) ◽  
pp. 59-72 ◽  
Author(s):  
Baoan Ji ◽  
Xue-qing Chen ◽  
David E. Misek ◽  
Rork Kuick ◽  
Samir Hanash ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Rt Pcr ◽  
Novel Genes ◽  
In Vivo Models ◽  
Severity Of The Disease ◽  
Deficient Mice

We hypothesized that genes expressed in pancreatic acinar cells during the initiation of acute pancreatitis determine the severity of the disease. Therefore, we utilized microarrays to identify those genes commonly induced in rat pancreatic acinar cells within 1–4 h in two in vivo models, caerulein and taurocholate administration. This strategy yielded 51 known genes representing a complex array of molecules, including those that are likely to either reduce or increase the severity of the disease. Novel genes identified in the current study included ATF3, BRF1, C/EBPβ, CGRP, EGR-1, ephrinA1, villin2, ferredoxin, latexin, lipocalin, MKP-1, NGFI-B, RhoA, tissue factor (TF), and syndecan. To validate these microarray results, the role of EGR-1 was further investigated using quantitative RT-PCR, Western blotting, and immunocytochemistry. EGR-1 expression occurred within acinar cells and correlated with the development of caerulein-induced acute pancreatitis in rats. Furthermore, the levels of the inflammation-related genes MCP-1, PAI, TF, IL-6, and ICAM-1 and the extent of lung inflammation were reduced during the initiation of caerulein-induced acute pancreatitis in EGR-1-deficient mice. Thus this study identified EGR-1 and several other novel genes likely to be important in the development and severity of acute pancreatitis.

scholarly journals Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells

2008 ◽  
Vol 181 (7) ◽  
pp. 1065-1072 ◽  
Author(s):  
Daisuke Hashimoto ◽  
Masaki Ohmuraya ◽  
Masahiko Hirota ◽  
Akitsugu Yamamoto ◽  
Koichi Suyama ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Knockout Mice ◽  
Early Stage ◽  
Acinar Cells ◽  
Conditional Knockout ◽  
Pancreatic Acinar Cells ◽  
Trypsinogen Activation ◽  
Conditional Knockout Mice ◽  
Cellular Environment

Autophagy is mostly a nonselective bulk degradation system within cells. Recent reports indicate that autophagy can act both as a protector and killer of the cell depending on the stage of the disease or the surrounding cellular environment (for review see Cuervo, A.M. 2004. Trends Cell Biol. 14:70–77). We found that cytoplasmic vacuoles induced in pancreatic acinar cells by experimental pancreatitis were autophagic in origin, as demonstrated by microtubule-associated protein 1 light chain 3 expression and electron microscopy experiments. To analyze the role of macroautophagy in acute pancreatitis, we produced conditional knockout mice lacking the autophagy-related 5 gene in acinar cells. Acute pancreatitis was not observed, except for very mild edema in a restricted area, in conditional knockout mice. Unexpectedly, trypsinogen activation was greatly reduced in the absence of autophagy. These results suggest that autophagy exerts devastating effects in pancreatic acinar cells by activation of trypsinogen to trypsin in the early stage of acute pancreatitis through delivering trypsinogen to the lysosome.

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.

scholarly journals Ubiquitin-Specific Protease 25 Aggravates Acute Pancreatitis and Acute Pancreatitis-Related Multiple Organ Injury by Destroying Tight Junctions Through Activation of The STAT3 Pathway

2022 ◽  
Vol 9 ◽  
Author(s):  
Zhengru Liu ◽  
Mingming Qi ◽  
Shan Tian ◽  
Qian Yang ◽  
Jian Liu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Tight Junctions ◽  
Multiple Organ ◽  
Organ Injury ◽  
Pancreatic Acinar Cells ◽  
Stat3 Pathway ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
Multiple Organ Injury

Ubiquitin-specific protease 25 (USP25) plays an important role in inflammation and immunity. However, the role of USP25 in acute pancreatitis (AP) is still unclear. To evaluate the role of USP25 in AP, we conducted research on clinical AP patients, USP25wild-type(WT)/USP25 knockout (USP25−/−) mice, and pancreatic acinar cells. Our results showed that serum USP25 concentration was higher in AP patients than in healthy controls and was positively correlated with disease severity. AP patients’ serum USP25 levels after treatment were significantly lower than that at the onset of AP. Moreover, USP25 expression was upregulated in cerulein-induced AP in mice, while USP25 deficiency attenuates AP and AP-related multiple organ injury. In vivo and in vitro studies showed that USP25 exacerbates AP by promoting the release of pro-inflammatory factors and destroying tight junctions of the pancreas. We showed that USP25 aggravates AP and AP-related multiple organ injury by activating the signal transducer and activator of transcription 3 (STAT3) pathway. Targeting the action of USP25 may present a potential therapeutic option for treating AP.

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

Phosphoinositide synthesis in desensitized rat pancreatic acinar cells

1995 ◽  
Vol 268 (6) ◽  
pp. G1043-G1050
Author(s):  
J. S. Lods ◽  
B. Rossignol ◽  
C. Dreux ◽  
J. Morisset
Keyword(s):  
Phorbol Ester ◽  
Inositol Trisphosphate ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Basal Rate ◽  
Phosphoinositide Turnover ◽  
Dose Dependent

To help understand the possible role of phosphoinositide turnover in the desensitization process, the availability of phosphatidylinositol 4,5-bisphosphate was investigated in normal and desensitized pancreatic acinar cells treated with carbamylcholine (Cch), caerulein (Cae), and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). In control acini, incorporation of [myo-3H]inositol into total phosphoinositides was maximal at 120 min, was Cch and Cae dose dependent, and was insensitive to TPA. Cch stimulation increased the proportion of [myo-3H]inositol incorporated into phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], whereas Cae specifically channeled [myo-3H]inositol incorporation into phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. In the desensitized cells, preexposure to Cch and Cae, but not to TPA, increased the subsequent basal rate of [myo-3H]inositol incorporation into total phosphoinositol (PI) by 66 and 50% above control values. There were no subsequent responses to increasing concentrations of Cch, Cae, and TPA during a second incubation. Desensitization of the pancreatic secretory responses to Cch, Cae, and TPA does not seem to result from a decrease either in total PI or in specific PtdIns(4,5)P2 synthesis, which is needed for inositol trisphosphate and diacylglycerol production.

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