Autophagy impairment in pancreatic acinar cells causes zymogen granule accumulation and pancreatitis

2018 ◽  
Vol 503 (4) ◽  
pp. 2576-2582 ◽  
Author(s):  
Kiyoshi Iwahashi ◽  
Hayato Hikita ◽  
Yuki Makino ◽  
Minoru Shigekawa ◽  
Kenji Ikezawa ◽  
...  
Keyword(s):  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Zymogen Granule

scholarly journals SYNTHESIS AND MIGRATION OF PROTEINS IN THE CELLS OF THE EXOCRINE PANCREAS AS REVEALED BY SPECIFIC ACTIVITY DETERMINATION FROM RADIOAUTOGRAPHS

1963 ◽  
Vol 16 (1) ◽  
pp. 1-23 ◽  
Author(s):  
H. Warshawsky ◽  
C. P. Leblond ◽  
B. Droz
Keyword(s):  
Specific Activity ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Zymogen Granule ◽  
Zymogen Granules ◽  
The Mean ◽  
And Migration ◽  
Rats And Mice ◽  
Silver Grains ◽  
Golgi Zone

Radioautographs of pancreatic acinar cells were prepared in rats and mice sacrificed at various times after injection of leucine-, glycine-, or methionine-H3. Measurements of radioactivity concentration (number of silver grains per unit area) and relative protein concentration (by microspectrophotometry of Millon-treated sections) yielded the mean specific activity of proteins in various regions of the acinar cells. The 2 to 5 minute radioautographs as well as the specific activity time curves demonstrate protein synthesis in ergastoplasm. From there, most newly synthesized proteins migrate to and accumulate in the Golgi zone. Then they spread to the whole zymogen region and, finally, enter the excretory ducts. An attempt at estimating turnover times indicated that two classes of proteins are synthesized in the ergastoplasm: "sedentary" with a slow turnover (62.5 hours) and "exportable" with rapid turnover (4.7 minutes). It is estimated that the exportable proteins spend approximately 11.7 minutes in the Golgi zone where they are built up into zymogen granules, and thereafter 36.0 minutes as fully formed zymogen granules, before they are released outside the acinar cell as pancreatic secretion. The mean life span of a zymogen granule in the cell is estimated to be 47.7 minutes.

High- and Small-Molecular-Weight GTP-Binding Proteins in Zymogen Granule Membranes of Rat Pancreatic Acinar Cells

1992 ◽  
Vol 2 (2) ◽  
pp. 77-89 ◽  
Author(s):  
Susanne Schnefel ◽  
Petra Zimmermann ◽  
André Pröfrock ◽  
Reinhard Jahn ◽  
Klaus Aktories ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Binding Proteins ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Zymogen Granule ◽  
Small Molecular Weight ◽  
Gtp Binding Proteins ◽  
Gtp Binding

Spatiotemporal analysis of exocytosis in mouse parotid acinar cells

2005 ◽  
Vol 289 (5) ◽  
pp. C1209-C1219 ◽  
Author(s):  
Ying Chen ◽  
Jennifer D. Warner ◽  
David I. Yule ◽  
David R. Giovannucci
Keyword(s):  
Acinar Cell ◽  
Digestive Enzyme ◽  
Acinar Cells ◽  
Optical Measurements ◽  
Pancreatic Acinar Cells ◽  
Second Phase ◽  
Zymogen Granule ◽  
Exocrine Cells ◽  
Parotid Acinar Cells ◽  
Camp Elevation

Exocrine cells of the digestive system are specialized to secrete protein and fluid in response to neuronal and/or hormonal input. Although morphologically similar, parotid and pancreatic acinar cells exhibit important functional divergence in Ca2+ signaling properties. To address whether there are fundamental differences in exocytotic release of digestive enzyme from exocrine cells of salivary gland versus pancreas, we applied electrophysiological and optical methods to investigate spatial and temporal characteristics of zymogen-containing secretory granule fusion at the single-acinar cell level by direct or agonist-induced Ca2+ and cAMP elevation. Temporally resolved membrane capacitance measurements revealed that two apparent phases of exocytosis were induced by Ca2+ elevation: a rapidly activated initial phase that could not be resolved as individual fusion events and a second phase that was activated after a delay, increased in a staircaselike fashion, was augmented by cAMP elevation, and likely reflected both sequential compound and multivesicular fusion of zymogen-containing granules. Optical measurements of exocytosis with time-differential imaging analysis revealed that zymogen granule fusion was induced after a minimum delay of ∼200 ms, occurred initially at apical and basolateral borders of acinar cells, and under strong stimulation proceeded from apical pole to deeper regions of the cell interior. Zymogen granule fusions appeared to coordinate subsequent fusions and produced persistent structures that generally lasted several minutes. In addition, parotid gland slices were used to assess secretory dynamics in a more physiological context. Parotid acinar cells were shown to exhibit both similar and divergent properties compared with the better-studied pancreatic acinar cell regarding spatial organization and kinetics of exocytotic fusion of zymogen granules.

Regulation of zymogen granule exocytosis by Ca2+, cAMP, and PKC in pancreatic acinar cells

2005 ◽  
Vol 334 (4) ◽  
pp. 1241-1247 ◽  
Author(s):  
Misun Lee ◽  
Sungkwon Chung ◽  
Dae Yong Uhm ◽  
Myoung Kyu Park
Keyword(s):  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Zymogen Granule ◽  
Granule Exocytosis

ZYMOGEN GRANULE EXOCYTOSIS IN RESPONSE TO DIRECT ACTIVATION OF CHOLECYSTOKININ RECEPTORS ON ISOLATED HUMAN PANCREATIC ACINAR CELLS

Pancreas ◽  
2007 ◽  
Vol 35 (4) ◽  
pp. 418-419
Author(s):  
J. A. Murphy ◽  
D. N. Criddle ◽  
M. Sherwood ◽  
M. Chvanov ◽  
E. Mclaughlin ◽  
...  
Keyword(s):  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Zymogen Granule ◽  
Granule Exocytosis ◽  
Direct Activation ◽  
Cholecystokinin Receptors

scholarly journals Dynamic Regulation of the Large Exocytotic Fusion Pore in Pancreatic Acinar Cells

2007 ◽  
Vol 18 (9) ◽  
pp. 3502-3511 ◽  
Author(s):  
Olga Larina ◽  
Purnima Bhat ◽  
James A. Pickett ◽  
Bradley S. Launikonis ◽  
Amit Shah ◽  
...  
Keyword(s):  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Fusion Pore ◽  
Secretory Cells ◽  
Zymogen Granule ◽  
Latrunculin B ◽  
Extracellular Solution ◽  
Dynamic Regulation ◽  
Pore Closure ◽  
Dependent Mechanism

Loss of granule content during exocytosis requires the opening of a fusion pore between the secretory granule and plasma membrane. In a variety of secretory cells, this fusion pore has now been shown to subsequently close. However, it is still unclear how pore closure is physiologically regulated and contentious as to how closure relates to granule content loss. Here, we examine the behavior of the fusion pore during zymogen granule exocytosis in pancreatic acinar cells. By using entry of high-molecular-weight dyes from the extracellular solution into the granule lumen, we show that the fusion pore has a diameter of 29–55 nm. We further show that by 5 min after granule fusion, many granules have a closed fusion pore with evidence indicating that pore closure is a prelude to endocytosis and that in granules with a closed fusion pore the chymotrypsinogen content is low. Finally, we show that latrunculin B treatment promotes pore closure, suggesting F-actin affects pore dynamics. Together, our data do not support the classical view in acinar cells that exocytosis ends with granule collapse. Instead, for many granules the fusion pore closes, probably as a transition to endocytosis, and likely involving an F-actin–dependent mechanism.

A novel zymogen granule protein (ZG29p) and the nuclear protein MTA1p are differentially expressed by alternative transcription initiation in pancreatic acinar cells of the rat

1999 ◽  
Vol 112 (15) ◽  
pp. 2539-2548
Author(s):  
R. Kleene ◽  
J. Zdzieblo ◽  
K. Wege ◽  
H.F. Kern
Keyword(s):  
Blot Analysis ◽  
Transcription Initiation ◽  
Northern Blot Analysis ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Zymogen Granule ◽  
Zymogen Granules ◽  
Rt Pcr ◽  
Rat Pancreas ◽  
Alternative Transcription

Using a polyclonal antibody against purified zymogen granule membrane components from rat pancreas a cDNA coding for the 29 kDa protein (ZG29p) was identified by immunoscreening of a hormonally stimulated pancreas cDNA library. Western blot analysis suggests that ZG29p is a pancreas-specific protein and immunofluorescence shows that ZG29p is mainly associated with zymogen granules. Analysis of subcellular fraction applying immunoblotting revealed that ZG29p was localized mainly in the soluble fraction of zymogen granules and in a Golgi- and RER-enriched fraction, but was absent from the cytosol. In isolated zymogen granule content ZG29p was associated with protein complexes containing amylase as main constituent. The cDNA coding for ZG29p is homologous to the C-terminal region of the candidate metastasis-associated gene mta1. Northern blot analysis and RT-PCR showed that no MTA1 mRNA is present in pancreas from fasted rats and in the rat pancreas carcinoma cell line AR4-2J in its protodifferentiated state. Although no ZG29p specific mRNA was seen in the northern blot analysis, RT-PCR showed that ZG29p was expressed under both non-stimulated and stimulated conditions. The expression of MTA1 was up-regulated in the pancreas by endogenous cholecystokinin release and in AR4-2J after induction of cellular differentiation by dexamethasone. Western blotting and immunofluorescense studies indicated that MTA1p is localized in the nucleus in all tissues studied. Using genomic DNA in PCR analysis it was shown that two short introns are present flanking the sequences of the 5′end of ZG29p cDNA. One intron contains consensus elements required for pancreas specific transcription initiation, suggesting that MTA1 and ZG29 are differentially expressed by alternative transcription initiation in the pancreas. The localisation of MTA1p in the nucleus of most cell types could signify a general role in gene regulation, while the cell type specific and exclusive expression of ZG29p in pancreatic acinar cells could indicate a role in granule formation.

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