scholarly journals Upregulation of dynamin II expression during the acquisition of a mature pancreatic acinar cell phenotype.

1996 ◽  
Vol 44 (12) ◽  
pp. 1373-1378 ◽  
Author(s):  
T A Cook ◽  
K J Mesa ◽  
B A Gebelein ◽  
R A Urrutia
Keyword(s):  
Acinar Cell ◽  
Growth Factor Receptor ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Cell Phenotype ◽  
Receptor Mediated Endocytosis ◽  
Ar42j Cells

Members of the dynamin superfamily are GTPases which have been shown to support receptor-mediated endocytosis in vivo and bind to growth factor receptor-associated proteins in vitro. In acinar cells of the pancreas, receptor-mediated endocytosis is very important for the recycling of membranes after secretory granule release. Therefore, characterization of the molecular machinery responsible for this process is critical for a better understanding of this phenomenon. In this study we sought to determine the expression pattern of the endocytic GTPase dynamin II during pancreatic acinar cell differentiation in developing rat embryos and in dexamethasone-treated AR42J cells using Western blot, Northern blot, and immunocytochemical analyses. During pancreatic development, dynamin immunoreactivity is almost undetectable until day E17 but undergoes significant upregulation in acinar cells starting at E18. In addition, the levels of dynamin mRNA and protein in AR42J cells increase approximately threefold during dexamethasone-induced acinar differentiation. The increase in dynamin levels that occurs in both embryonic pancreatic cells and dexamethasone-treated AR42J cells correlates with the establishment of a more differentiated acinar phenotype. Therefore, these results suggest a potential role for dynamin in supporting receptor-mediated endocytosis in mature pancreatic acinar cells.

scholarly journals MECOM permits pancreatic acinar cell dedifferentiation avoiding cell death under stress conditions

2020 ◽  
Author(s):  
Elyne Backx ◽  
Elke Wauters ◽  
Jonathan Baldan ◽  
Mathias Van Bulck ◽  
Ellis Michiels ◽  
...  
Keyword(s):  
Cell Death ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Stress Conditions ◽  
Loss Of Function ◽  
Cell Dedifferentiation ◽  
Duct Cells

ABSTRACTMaintenance of the pancreatic acinar cell phenotype suppresses tumor formation. Hence, repetitive acute or chronic pancreatitis, stress conditions in which the acinar cells dedifferentiate, predispose for cancer formation in the pancreas. Dedifferentiated acinar cells acquire a large panel of duct cell specific markers. However, it remains unclear to what extent dedifferentiated acini differ from native duct cells and which genes are uniquely regulating acinar cell dedifferentiation. Moreover, most studies have been performed in mouse since the availability of human cells is scarce.Here, we applied a non-genetic lineage tracing method in our culture model of human pancreatic exocrine cells that allowed cell-type specific gene expression profiling by RNA sequencing. Subsequent to this discovery analysis, one transcription factor that was unique for dedifferentiated acinar cells was functionally characterized using in vitro and in vivo genetic loss-of-function experimental models.RNA sequencing analysis showed that human dedifferentiated acinar cells expressed genes in ‘Pathways of cancer’ with prominence of the transcription factor MECOM (EVI-1) that was absent from duct cells. During mouse embryonic development, pre-acinar cells transiently expressed MECOM and MECOM was re-expressed in experimental in vivo models of acute and chronic pancreatitis in vivo, conditions in which acinar cells dedifferentiate. MECOM expression correlated with and was directly regulated by SOX9. MECOM loss-of-function in mouse acinar cells in vitro and in vivo impaired cell adhesion resulting in more prominent acinar cell death and suppressed acinar cell dedifferentiation by limiting ERK signaling.In conclusion, we transcriptionally profiled the two major human pancreatic exocrine cell types, acinar and duct cells, during experimental stress conditions. We provide insights that in dedifferentiated acinar cells, cancer pathways are upregulated in which MECOM is a critical regulator that suppresses acinar cell death by permitting cellular dedifferentiation.

MiR-155 aggravates impaired autophagy of pancreatic acinar cells through targeting Rictor

2020 ◽  
Vol 52 (2) ◽  
pp. 192-199 ◽  
Author(s):  
Xueming Zhang ◽  
Jiangtao Chu ◽  
Haijun Sun ◽  
Dali Zhao ◽  
Biao Ma ◽  
...  
Keyword(s):  
Acinar Cells ◽  
Immunofluorescence Assay ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Luciferase Reporter ◽  
Cellular Model ◽  
Protein Levels ◽  
Ar42j Cells ◽  
Direct Target ◽  
Dual Luciferase Reporter Assay

Abstract The aim of this study was to investigate the role and mechanism of miR-155 in regulating autophagy in a caerulein-induced acute pancreatitis (AP) cellular model. GFP-LC3 immunofluorescence assay was performed to detect autophagy vesicle formation in pancreatic acinar cell line AR42J. AR42J cells were transfected with miR-155 mimic, inhibitor, and corresponding controls to explore the effect of miR-155 on autophagy. The protein levels of LC3-I, LC3-II, Beclin-1, and p62 were analyzed by western blot analysis. Dual-luciferase reporter assay was performed to verify the interaction between miR-155 and Rictor (RPTOR independent companion of MTOR complex 2). The results showed that caerulein treatment induced impaired autophagy as evidenced by an increase in the accumulation of p62 together with LC3-II in AR42J cells, accompanied by miR-155 upregulation. Furthermore, miR-155 overexpression aggravated, whereas miR-155 silencing reduced the caerulein-induced impairment of autophagy. Mechanistically, Rictor was confirmed to be a direct target of miR-155, which could rescue the miR-155 overexpression-mediated aggravation of impaired autophagy. Collectively, these findings indicate that miR-155 aggravates impaired autophagy in caerulein-treated pancreatic acinar cells by targeting Rictor.

Crambene induces pancreatic acinar cell apoptosis via the activation of mitochondrial pathway

2006 ◽  
Vol 291 (1) ◽  
pp. G95-G101 ◽  
Author(s):  
Yang Cao ◽  
Sharmila Adhikari ◽  
Abel Damien Ang ◽  
Marie Véronique Clément ◽  
Matthew Wallig ◽  
...  
Keyword(s):  
Acinar Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Fas Ligand ◽  
Annexin V ◽  
Acinar Cells ◽  
Mitochondrial Pathway ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Pancreatic Acini

We investigated the apoptotic pathway activated by crambene (1-cyano-2-hydroxy-3-butene), a plant nitrile, on pancreatic acinar cells. As evidenced by annexin V-FITC staining, crambene treatment for 3 h induced the apoptosis but not necrosis of pancreatic acini. Caspase-3, -8, and -9 activities in acini treated with crambene were significantly higher than in untreated acini. Treatment with caspase-3, -8, and -9 inhibitors inhibited annexin V staining, as well as caspase-3 activity, pointing to an important role of these caspases in crambene-induced acinar cell apoptosis. The mitochondrial membrane potential was collapsed, and cytochrome c was released from the mitochondria in crambene-treated acini. Neither TNF-α nor Fas ligand levels were changed in pancreatic acinar cells after crambene treatment. These results provide evidence for the induction of pancreatic acinar cell apoptosis in vitro by crambene and suggest the involvement of mitochondrial pathway in pancreatic acinar cell apoptosis.

scholarly journals Expression of Clusterin in Pancreatic Acinar Cell Injuries In Vivo and In Vitro

Pancreas ◽  
2001 ◽  
Vol 22 (2) ◽  
pp. 126-134 ◽  
Author(s):  
Min-Jue Xie ◽  
Yoshiharu Motoo ◽  
Shi-Bing Su ◽  
Norio Sawabu
Keyword(s):  
Acinar Cell ◽  
Pancreatic Acinar Cell

Effects of pancreatic acinar cell surface antibodies and complement on isolated rat acinar cells in vitro

1988 ◽  
Vol 55 (1) ◽  
Author(s):  
H. -U. Schulz ◽  
G. Letko ◽  
H. -J. Hass ◽  
H. Spormann ◽  
P. Kemnitz ◽  
...  
Keyword(s):  
Cell Surface ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Surface Antibodies ◽  
Isolated Rat

Multiple isoforms of the ryanodine receptor are expressed in rat pancreatic acinar cells

2000 ◽  
Vol 351 (1) ◽  
pp. 265-271 ◽  
Author(s):  
Timothy J. FITZSIMMONS ◽  
Ilya GUKOVSKY ◽  
James A. McROBERTS ◽  
Edward RODRIGUEZ ◽  
F. Anthony LAI ◽  
...  
Keyword(s):  
Western Blot ◽  
Ryanodine Receptor ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Protein Band ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Rt Pcr ◽  
Pancreatic Acini ◽  
Cell Functions

Regulation of cytosolic Ca2+ is important for a variety of cell functions. The ryanodine receptor (RyR) is a Ca2+ channel that conducts Ca2+ from internal pools to the cytoplasm. To demonstrate the presence of the RyR in the pancreatic acinar cell, we performed reverse transcriptase (RT)-PCR, Western blot, immunocytochemistry and microscopic Ca2+-release measurements on these cells. RT-PCR showed the presence of mRNA for RyR isoforms 1, 2 and 3 in both rat pancreas and dispersed pancreatic acini. Furthermore, mRNA expression for RyR isoforms 1 and 2 was demonstrated by RT-PCR in individual pancreatic acinar cells selected under the microscope. Western-blot analysis of acinar cell immunoprecipitates, using antibodies against RyR1 and RyR2, showed a high-molecular-mass (> 250kDa) protein band that was much less intense when immunoprecipitated in the presence of RyR peptide. Functionally, permeablized acinar cells stimulated with the RyR activator, palmitoyl-CoA, released Ca2+ from both basolateral and apical regions. These data show that pancreatic acinar cells express multiple isoforms of the RyR and that there are functional receptors throughout the cell.

scholarly journals SEC23B is required for pancreatic acinar cell function in adult mice

2017 ◽  
Vol 28 (15) ◽  
pp. 2146-2154 ◽  
Author(s):  
Rami Khoriaty ◽  
Nancy Vogel ◽  
Mark J. Hoenerhoff ◽  
M. Dolors Sans ◽  
Guojing Zhu ◽  
...  
Keyword(s):  
Acinar Cell ◽  
Cell Function ◽  
Acinar Cells ◽  
Cell Loss ◽  
Normal Function ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Total Protein Content ◽  
Pancreatic Cell ◽  
Adult Mice

Mice with germline absence of SEC23B die perinatally, exhibiting massive pancreatic degeneration. We generated mice with tamoxifen-inducible, pancreatic acinar cell–specific Sec23b deletion. Inactivation of Sec23b exclusively in the pancreatic acinar cells of adult mice results in decreased overall pancreatic weights from pancreatic cell loss (decreased pancreatic DNA, RNA, and total protein content), as well as degeneration of exocrine cells, decreased zymogen granules, and alterations in the endoplasmic reticulum (ER), ranging from vesicular ER to markedly expanded cisternae with accumulation of moderate-density content or intracisternal granules. Acinar Sec23b deletion results in induction of ER stress and increased apoptosis in the pancreas, potentially explaining the loss of pancreatic cells and decreased pancreatic weight. These findings demonstrate that SEC23B is required for normal function of pancreatic acinar cells in adult mice.

scholarly journals Morphometric Measurements to Quantify the Cerulein Induced Hyperstimulatory Pancreatitis of Rats under the Protective Effect of Lectins

1998 ◽  
Vol 17 (4) ◽  
pp. 219-230 ◽  
Author(s):  
Ludwig Jonas ◽  
Ulrike Mikkat ◽  
Anke Witte ◽  
Uta Beckmann ◽  
Katrin Dölker ◽  
...  
Keyword(s):  
Protective Effect ◽  
Amylase Activity ◽  
Acinar Cells ◽  
Inhibitory Effect ◽  
Pancreatic Acinar Cells ◽  
Amylase Secretion ◽  
Ulex Europaeus ◽  
Serum Amylase Activity

In preceding papers we demonstrated an inhibitory effect of wheat germ agglutinin (WGA) and Ulex europaeus agglutinin (UEA) on the cholecystokinin (CCK) binding to the CCK receptor of rat pancreatic cells and also on the CCK induced Ca2+release and α-amylase secretionin vitroas well as on pancreatic secretion of intact ratsin vivo. In the present study we show the same inhibitory effect of both lectins on the cerulein pancreatitis of rats. This acute pancreatitis was induced by supramaximal injections (5 µg/kg/h iv or 10 µg/kg/h ip) of the CCK analogue cerulein in rats every hour. To monitor the degree of pancreatitis, we measured the number and diameter of injury vacuoles in the pancreatic acinar cells as one of the most important signs of this type of pancreatitis by light microscopic morphometry with two different systems on paraffin sections. Furthermore, the serum α-amylase activity was measured biochemically. We found a correlation between the diameter of vacuoles inside the acinar cells and the serum enzyme activity up to 24 h. The simultaneous ip administration of cerulein and WGA or UEA in a dosage of 125 µg/kg/h for 8 h led to a reduction of vacuolar diameter from 13.1 ± 2.0 µm (cerulein) to 7.5 ± 1.1 µm (cerulein + WGA) or 7.2 ± 1.3 µm (cerulein + UEA). The serum amylase activity was reduced from 63.7 ± 15.8 mmol/l \times min (cerulein) to 37.7 ± 11.8 (cerulein + WGA) or 39.4; +52.9; -31.1 (cerulein + UEA-I). Both parameters allow the grading this special type of pancreatitis to demonstrate the protective effect of the lectins.

scholarly journals Enhanced Secretion of Amylase from Exocrine Pancreas of Connexin32-deficient Mice

1998 ◽  
Vol 141 (5) ◽  
pp. 1267-1275 ◽  
Author(s):  
Marc Chanson ◽  
Marjorie Fanjul ◽  
Domenico Bosco ◽  
Eric Nelles ◽  
Susanne Suter ◽  
...  
Keyword(s):  
Acinar Cell ◽  
Intercellular Communication ◽  
Plaque Assay ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Amylase Secretion ◽  
Wild Type ◽  
Patch Clamp Recording ◽  
Junctional Communication

To determine whether junctional communication between pancreatic acinar cells contributes to their secretory function in vivo, we have compared wild-type mice, which express the gap junctional proteins connexin32 (Cx32) and connexin26, to mice deficient for the Cx32 gene. Pancreatic acinar cells from Cx32 (−/−) mice failed to express Cx32 as evidenced by reverse transcription–PCR and immunolabeling and showed a marked reduction (4.8- and 25-fold, respectively) in the number and size of gap junctions. Dye transfer studies showed that the extent of intercellular communication was inhibited in Cx32 (−/−) acini. However, electrical coupling was detected by dual patch clamp recording in Cx32 (−/−) acinar cell pairs. Although wild-type and Cx32 (−/−) acini were similarly stimulated to release amylase by carbamylcholine, Cx32 (−/−) acini showed a twofold increase of their basal secretion. This effect was caused by an increase in the proportion of secreting acini, as detected with a reverse hemolytic plaque assay. Blood measurements further revealed that Cx32 (−/−) mice had elevated basal levels of circulating amylase. The results, which demonstrate an inverse relationship between the extent of acinar cell coupling and basal amylase secretion in vivo, support the view that the physiological recruitment of secretory acinar cells is regulated by gap junction mediated intercellular communication.

scholarly journals Monoclonal antibodies as probes for plasma membrane domains in the exocrine pancreas.

1988 ◽  
Vol 36 (8) ◽  
pp. 1043-1051 ◽  
Author(s):  
R C De Lisle ◽  
C D Logsdon ◽  
S R Hootman ◽  
J A Williams
Keyword(s):  
Monoclonal Antibodies ◽  
Acinar Cell ◽  
Apical Membrane ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Apical Surface ◽  
Membrane Domains ◽  
Monolayer Cultures ◽  
Apical Membranes

Monoclonal antibodies (mAb) were generated as probes for the plasma membrane domains of pancreatic acinar cells. Primary monolayer cultures of mouse pancreatic acinar cells, which have an expanded apical surface relative to normal pancreas, were used to immunize rats. With conventional immunization and fusion protocols, 3% of the hybridomas were positive against the acinar lumen by indirect immunofluorescence of mouse pancreas cryosections. Culturing of spleen cells from an immunized rat on the apical surface of acinar cell monolayer cultures before fusion with the myeloma (an in vitro boost) doubled the percentage of hybridomas producing apical membrane-specific mAb. Monoclonal antibodies were characterized by immunofluorescence, ultrastructural immunoperoxidase cytochemistry, immunoprecipitation, and immunoblotting. One antibody, acinar-1 (IgG2a), labeled the apical membranes of pancreatic acinar cells, hepatocytes, salivary and lacrimal gland acinar cells, and the brush border of small intestine enterocytes. This mAb precipitated and blotted a protein of 94 KD. Acinar-2 (IgM) also labeled pancreatic acinar cell apical membranes but did not label other tissues and did not precipitate or blot. Acinar-3 labeled pancreatic acinar cell lateral membranes. Duct-1 (IgM) labeled pancreatic duct apical membrane and ducts in liver and salivary glands but did not precipitate or blot. These domain-specific mAb demonstrate that common antigenic determinants occur in the apical surfaces of several exocrine epithelia and may be important in secretion.

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