期刊
JOURNAL OF PROTEOMICS
卷 111, 期 -, 页码 238-248出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jprot.2014.03.043
关键词
Intracellular peptides; Neurolysin; Hemopressin; Peptide metabolism; Endopeptidase; Oligopeptidase
资金
- Pro-Reitoria de Pesquisa, University of Sao Paulo through the Support Center for Research in Proteolysis and Cell Signaling (NAPPS) [2012.1.17607.1.2]
- Brazilian National Research Council (CNPq) [559698/2009-7]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP
- Projeto Tematico) [04/04933-2]
- CNPq research fellowships
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 significance Neurolysin 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据