Exposure of cultured fibroblasts to the peptide PR-11 for the identification of induced proteome alterations and discovery of novel potential ligands.

Autor:	Breguez GS; Programa de Pós-Graduação em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Neves LX; Programa de Pós-Graduação em Biotecnologia, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Silva KTS; Departamento de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., de Freitas LMA; Programa de Pós-Graduação em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., de Oliveira Faria G; Programa de Pós-Graduação em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Isoldi MC; Departamento de Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Castro-Borges W; Departamento de Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., de Andrade MHG; Departamento de Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil. Electronic address: miltonguerra00@gmail.com.
Jazyk:	angličtina
Zdroj:	Biochimica et biophysica acta [Biochim Biophys Acta] 2016 Dec; Vol. 1864 (12), pp. 1775-1786. Date of Electronic Publication: 2016 Sep 28.
DOI:	10.1016/j.bbapap.2016.09.017
Abstrakt:	The PR-11 peptide corresponds to the N-terminal and active region of the endogenously synthesized PR-39 molecule, of porcine origin. It is known to possess various biological effects including antimicrobial properties, angiogenic and anti-inflammatory activities. Apart from its reported activity as a proteasome inhibitor, a more comprehensive understanding of its function, at the molecular level, is still lacking. In this study, we used a label-free shotgun strategy to evaluate the proteomic alterations caused by exposure of cultured fibroblasts to the peptide PR-11. This approach revealed that more than half of the identified molecules were related to signalling, transcription and translation. Proteins directly associated to regulation of angiogenesis and interaction with the hypoxia-inducible factor 1-α (HIF-1α) were significantly altered. In addition, at least three differentially expressed molecules of the NF-κB pathway were detected, suggesting an anti-inflammatory property of PR-11. At last, we demonstrated novel potential ligands of PR-11, through its immobilization for affinity chromatography. Among the eluted molecules, gC1qR, a known complement receptor, appeared markedly enriched. This provided preliminary evidence of a PR-11 ligand possibly involved in the internalization of this peptide. Altogether, our findings contributed to a better understanding of the cellular pathways affected by PR-39 derived molecules. (Copyright © 2016 Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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