Severe acute pancreatitis and reduced acinar cell apoptosis in the exocrine pancreas of mice deficient for the Cx32 gene.

Details

Serval ID
serval:BIB_2B83C739D7DF
Type
Article: article from journal or magazin.
Collection
Publications
Title
Severe acute pancreatitis and reduced acinar cell apoptosis in the exocrine pancreas of mice deficient for the Cx32 gene.
Journal
Gastroenterology
Author(s)
Frossard J.L., Rubbia-Brandt L., Wallig M.A., Benathan M., Ott T., Morel P., Hadengue A., Suter S., Willecke K., Chanson M.
ISSN
0016-5085
Publication state
Published
Issued date
02/2003
Peer-reviewed
Oui
Volume
124
Number
2
Pages
481-493
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
BACKGROUND & AIMS: The early events leading to acinar cell injury during acute pancreatitis are poorly characterized. Signaling through gap junction channels contributes to the homeostasis of the exocrine pancreas by coordinating acinar cell activity within an acinus. To explore the role of gap junctional communication in acinar cell response to injury, we analyzed the course of acute pancreatitis induced by injection of cerulein in mice deficient for Cx32, the major gap junction protein expressed in the exocrine pancreas. METHODS: The severity of pancreatitis was evidenced by measuring serum amylase activity, pancreatic edema, acinar cell necrosis, pancreatic tumor necrosis factor alpha concentration, and myeloperoxidase activity. Acinar cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL), caspase-3 activity, and Bax/Bcl-2 expression. Expression and function of connexin were evaluated by immunofluorescence and dye coupling. RESULTS: Cx32-deficient mice exhibited a deleterious course of acute pancreatitis with increased necrosis, edema, and inflammation of the exocrine pancreas. In addition, the exocrine pancreas of Cx32-deficient mice showed a decreased number of TUNEL-positive acinar cells and decreased caspase-3 activity but no change in Bax or Bcl-2 pancreatic expression. Interestingly, chemicals known to induce apoptosis in vivo had no effect on Cx32-deficient pancreatic acinar cells. CONCLUSIONS: Deficiency of a pancreatic connexin converts a mild reversible form of acute pancreatitis into a severe disease and decreases the sensitivity of acinar cells to apoptotic stimuli. The results show that acinar cell-to-cell communication plays a key role in the modulation of severity of acute pancreatitis.
Keywords
Acute Disease, Animals, Apoptosis, Caerulein, Connexins, Glutathione, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Knockout, Pancreas, Pancreatitis, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Severity of Illness Index, bcl-2-Associated X Protein
Pubmed
Web of science
Create date
28/01/2008 9:20
Last modification date
20/08/2019 14:10
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