Publication
Title
Four day inhibition of prolyl oligopeptidase causes significant changes in the peptidome of rat brain, liver and kidney
Author
Abstract
Prolyl oligopeptidase (PREP) cleaves short peptides at the C-side of proline. Although several proline containing neuropeptides have been shown to be efficiently cleaved by PREP in vitro, the actual physiological substrates of this peptidase are still a matter of controversy. The aim of this study was to evaluate the changes in the peptidome of rat tissues caused by a repeated 4-day administration of the potent and specific PREP inhibitor KYP-2047, using our recently developed iTRAQ-based technique. We found tissue-dependent changes in the levels of specific subsets of peptides mainly derived from cytosolic proteins. Particularly in the kidney, where the levels of cytochrome c oxidase were found decreased, many of the altered peptides originated from mitochondrial proteins being involved in energy metabolism. However, in the hypothalamus, we found significant changes in peptides derived front hormone precursors. We could not confirm a role of PREP as the metabolising enzyme for beta-endorphin, galanin, octadecaneuropeptide, neuropeptide-glutamic acid-isoleucine, substance P. somatostatin, enkephalin and neuropeptide Y. Furthermore, changes in the degradation patterns of some of these neuropeptides, and also most of those derived from other larger proteins, did not follow specificity to proline. After a 4-day treatment, we found a significant amount of peptides, all derived from secreted pro-proteins, being cleaved with pair of basic residue specificity. In vitro experiments indicated that PREP modifies the endogenous dibasic residue specific proteolysis, in a KYP-2047 sensitive v/ay. These findings suggest that PREP may act indirectly within the routes leading to the specific peptide changes that we observed. The data reported here suggest a wider tissue specific physiological role of l'REP rather than the mere metabolism of proline containing active peptides and hormones. (C) 2012 Elsevier Masson SAS. All rights reserved.
Language
English
Source (journal)
Biochimie / Société de chimie biologique [Paris] - Paris
Publication
Paris : 2012
ISSN
0300-9084
Volume/pages
94:9(2012), p. 1849-1859
ISI
000307087900002
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 09.10.2012
Last edited 15.07.2017
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