Peptidomic analysis of the neurolysin-knockout mouse brain
Nenhuma Miniatura disponível
Data
2014-12-05
Autores
Castro, Leandro M. [UNIFESP]
Cavalcanti, Diogo M. L. P.
Araujo, Christiane B.
Rioli, Vanessa
Icimoto, Marcelo Y. [UNIFESP]
Gozzo, Fabio C.
Juliano, Maria [UNIFESP]
Juliano, Luiz [UNIFESP]
Oliveira, Vitor [UNIFESP]
Ferro, Emer S.
Orientadores
Tipo
Artigo
Título da Revista
ISSN da Revista
Título de Volume
Resumo
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.
Descrição
Citação
Journal of Proteomics. Amsterdam: Elsevier B.V., v. 111, p. 238-248, 2014.