BACE1 is a newly discovered protein secreted by the pancreas which cleaves enteropeptidase in vitro.
BACKGROUND
Activity of beta-site APP-cleaving enzyme1 (BACE1) is required for the generation of beta-amyloid peptides, the principal constituents of plaques in the brains of patients with Alzheimer's disease. Strong BACE1 expression has also been described in pancreatic tissue.


OBJECTIVE
The aim of the present study was to reveal the cell type-specific expression of BACE1 in the pancreas and to identify a substrate for BACE1 in this organ.


METHODS
RT-PCR of microdissected rat pancreatic tissue was carried out in order to analyze BACE1 expression within pancreatic acini. Pancreatic juice was examined by western blot analysis and by an enzymatic activity assay in order to reveal the presence of secreted BACE1. Database analysis suggested enteropeptidase as a putative substrate for BACE1 in pancreatic juice. In vitro digestion of enteropeptidase by BACE1 was performed to demonstrate this cleavage.


RESULTS
We demonstrate the expression of BACE1 in the islets of Langerhans and at the apical pole of pancreatic acinar cells. Recombinant BACE1 cleaves enteropeptidase in vitro. Furthermore, some results suggested the presence of BACE1 enzymatic activity in pancreatic juice and pancreatic tissue.


CONCLUSIONS
We hypothesize that enteropeptidase is a BACE1 substrate in vivo. If so, BACE1 could protect the pancreas from premature trypsinogen activation due to the occasionally occurring reflux of enteropeptidase.
Hoffmeister
Albrecht
A
Department of Internal Medicine II, University of Leipzig, Leipzig, Germany. albrecht.hoffmeister@medizin.uni-leipzig.de
Dietz
Gunther
G
Zeitschel
Ulrike
U
Mössner
Joachim
J
Rossner
Steffen
S
Stahl
Tobias
T
D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004765:Enteropeptidase / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D010179:Pancreas / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D013379:Substrate Specificity; D014018:Tissue Distribution
D053829:Amyloid Precursor Protein Secretases; D004765:Enteropeptidase; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat