AGH is a new hemoglobin alpha-chain fragment with antinociceptive activity

AGH is a new hemoglobin alpha-chain fragment with antinociceptive activity

Author Ribeiro, Natalia M. Google Scholar
Toniolo, Elaine F. Google Scholar
Castro, Leandro M. Autor UNIFESP Google Scholar
Russo, Lilian C. Google Scholar
Rioli, Vanessa Google Scholar
Ferro, Emer S. Google Scholar
Dale, Camila S. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Butantan Inst
Abstract Limited proteolysis of certain proteins leads to the release of endogenous bioactive peptides. Hemoglobin-derived peptides such as hemorphins and hemopressins are examples of intracellular protein-derived peptides that have antinociceptive effects by modulating G-protein coupled receptors activities. in the present study, a previously characterized substrate capture assay that uses a catalytically inactive form of the thimet oligopeptidase was combined with isotopic labeling and mass spectrometry in order to identify new bioactive peptides. Indeed, we have identified the peptide AGHLDDLPGALSAL (AGH), a fragment of the hemoglobin alpha-chain, which specifically bind to the inactive thimet oligopeptidase in the substrate capture assay. Previous peptidomics studies have identified the AGH as well as many other natural peptides derived from hemoglobin alpha-chain containing this sequence, further suggesting that AGH is a natural endogenous peptide. Pharmacological assays suggest that AGH inhibits peripheral inflammatory hyperalgesic responses through indirect activation of mu opioid receptors, without having a central nervous system activity. Therefore, we have successfully used the substrate capture assay to identify a new endogenous bioactive peptide derived from hemoglobin alpha-chain. (C) 2013 Elsevier Inc. All rights reserved.
Keywords Hemoglobin-derived peptides
Hemopressin
Opioid
Inflammation
Hyperalgesia
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Pro-reitoria de Pesquisa, University of São Paulo through the Nucleo de Apoio a Pesquisa na Interface Proteolise-Sinalizacao Celular (NAPPS)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number CNPq: 559698/2009-7
Pro-reitoria de Pesquisa, University of São Paulo through the Nucleo de Apoio a Pesquisa na Interface Proteolise-Sinalizacao Celular (NAPPS): 2012.1.17607.1.2
Date 2013-10-01
Published in Peptides. New York: Elsevier B.V., v. 48, p. 10-20, 2013.
ISSN 0196-9781 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 10-20
Origin http://dx.doi.org/10.1016/j.peptides.2013.07.011
Access rights Closed access
Type Article
Web of Science ID WOS:000324998300002
URI http://repositorio.unifesp.br/handle/11600/36837

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