Publication
Title
Kinetic study of neuropeptide Y (NPY) proteolysis in blood and identification of NPY$_{3-35}: a new peptide generated by plasma kallikrein
Author
Abstract
There is little information on how neuropeptide Y (NPY) proteolysis by peptidases occurs in serum, in part because reliable techniques are lacking to distinguish different NPY immunoreactive forms and also because the factors affecting the expression of these enzymes have been poorly studied. In the present study, LC-MS/MS was used to identify and quantify NPY fragments resulting from peptidolytic cleavage of NPY136 upon incubation with human serum. Kinetic studies indicated that NPY136 is rapidly cleaved in serum into 3 main fragments with the following order of efficacy: NPY336 ≫ NPY335 > NPY236. Trace amounts of additional NPY forms were identified by accurate mass spectrometry. Specific inhibitors of dipeptidyl peptidase IV, kallikrein, and aminopeptidase P prevented the production of NPY336, NPY335, and NPY236, respectively. Plasma kallikrein at physiological concentrations converted NPY336 into NPY335. Receptor binding assays revealed that NPY335 is unable to bind to NPY Y1, Y2, and Y5 receptors; thus NPY335 may represent the major metabolic clearance product of the Y2/Y5 agonist, NPY336.
Language
English
Source (journal)
Journal of biological chemistry. - Baltimore, Md
Publication
Baltimore, Md : 2009
ISSN
0021-9258
Volume/pages
284:37(2009), p. 24715-24724
ISI
000269734000006
Full text (Publishers DOI)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 15.01.2010
Last edited 19.05.2017
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