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- Title
Loss of Bace1 in Mice Does Not Alter the Severity of Caerulein Induced Pancreatitis.
- Authors
Heindl, Mario; Tuennemann, Jan; Sommerer, Ines; Mössner, Joachim; Hoffmeister, Albrecht
- Abstract
Context: Beta-site alpha-amyloid protein cleaving enzyme1 (BACE1) plays a key role in the pathogenesis of Alzheimer’s disease. Additional to its moderate expression in the brain, high levels of BACE1 mRNA were found in the pancreas. Murine Bace1 has been immunohistochemicaly detected at the apical pole of acinar cells within the exocrine pancreas of mice and Bace1 activity was observed in pancreatic juice. In vitro experiments revealed enteropeptidase as a putative substrate for Bace1 suggesting a role in acute pancreatitis. Objective: The aim of this study was to address a protective mechanism of Bace1 in acute experimental pancreatitis in mice. Methods: Acute experimental pancreatitis was induced by intraperitoneal injection of caerulein in homozygote Bace1-/- mice and wild type mice. Serum and tissue analyses were carried out after 4 h, 8 h and 24 h. Measurement of plasma amylase and lipase was performed to confirm pancreatitis induction. In order to assess the severity of pancreatitis H&E stained pancreatic sections were examined regarding edema, inflammation and apoptosis. Immunohistochemical detection of myeloperoxidase (MPO) positive cells was carried out to further quantify the extent of inflammation. Expression of Bace2 within the pancreas was analyzed by immunohistochemistry and RT-qPCR. Results: We demonstrate that total loss of Bace1 in mice leads to no alterations in the course of acute experimental caerulein-pancreatitis. Bace1-/- mice develop a moderate pancreatitis that is comparable in histomorphological and serological features with those seen in wild type mice. Discussion: We discuss the results in the context of the applied caerulein induced edematous pancreatitis model and possible compensatory mechanisms via Bace2 that might be responsible for the observed results.
- Subjects
PANCREATITIS; CERULETIDE; AMYLOID beta-protein; ALZHEIMER'S disease; IMMUNOHISTOCHEMISTRY; LABORATORY mice
- Publication
PLoS ONE, 2015, Vol 10, Issue 5, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0125556