Peptidomic analysis of the neurolysin-knockout mouse brain

Peptidomic analysis of the neurolysin-knockout mouse brain

Author Castro, Leandro M. Autor UNIFESP Google Scholar
Cavalcanti, Diogo M. L. P. Google Scholar
Araujo, Christiane B. Google Scholar
Rioli, Vanessa Google Scholar
Icimoto, Marcelo Y. Autor UNIFESP Google Scholar
Gozzo, Fabio C. Google Scholar
Juliano, Maria Autor UNIFESP Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Oliveira, Vitor Autor UNIFESP Google Scholar
Ferro, Emer S. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
LETA CETICS
Universidade Estadual de Campinas (UNICAMP)
Abstract A large number of intracellular peptides are constantly produced following protein degradation by the proteasome. A few of these peptides function in cell signaling and regulate protein protein interactions. Neurolysin (Nln) is a structurally defined and biochemically well-characterized endooligopeptidase, and its subcellular distribution and biological activity in the vertebrate brain have been previously investigated. However, the contribution of Nln to peptide metabolism in vivo is poorly understood. in this study, we used quantitative mass spectrometry to investigate the brain peptidome of Nln-knockout mice. An additional in vitro digestion assay with recombinant Nln was also performed to confirm the identification of the substrates and/or products of Nln. Altogether, the data presented suggest that Nln is a key enzyme in the in vivo degradation of only a few peptides derived from proenkephalin, such as Met-enkephalin and octapeptide. Nln was found to have only a minor contribution to the intracellular peptide metabolism in the entire mouse brain. However, further studies appear necessary to investigate the contribution of Nln to the peptide metabolism in specific areas of the murine brain.Biological significanceNeurolysin was first identified in the synaptic membranes of the rat brain in the middle 80's by Frederic Cheder and colleagues. Neurolysin was well characterized biochemically, and its brain distribution has been confirmed by immunohistochemical methods. the neurolysin contribution to the central and peripheral neurotensin-mediated functions in vivo has been delineated through inhibitor-based pharmacological approaches, but its genuine contribution to the physiological inactivation of neuropeptides remains to be firmly established. As a result, the main significance of this work is the first characterization of the brain peptidome of the neurolysin-knockout mouse. (C) 2014 Published by Elsevier B.V.
Keywords Intracellular peptides
Neurolysin
Hemopressin
Peptide metabolism
Endopeptidase
Oligopeptidase
Language English
Sponsor Pro-Reitoria de Pesquisa, University of São Paulo through the Support Center for Research in Proteolysis and Cell Signaling (NAPPS)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number Pro-Reitoria de Pesquisa, University of São Paulo through the Support Center for Research in Proteolysis and Cell Signaling (NAPPS): 2012.1.17607.1.2
CNPq: 559698/2009-7
FAPESP: 04/04933-2
Date 2014-12-05
Published in Journal of Proteomics. Amsterdam: Elsevier B.V., v. 111, p. 238-248, 2014.
ISSN 1874-3919 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 238-248
Origin http://dx.doi.org/10.1016/j.jprot.2014.03.043
Access rights Closed access
Type Article
Web of Science ID WOS:000345949300019
URI http://repositorio.unifesp.br/handle/11600/38548

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