Exposure of cultured fibroblasts to the peptide PR-11 for the identification of induced proteome alterations and discovery of novel potential ligands.
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.
['Breguez|Gustavo Silveira|GS|', 'Neves|Leandro Xavier|LX|', 'Silva|Karina Taciana Santos|KTS|', 'de Freitas|Lorran Miranda Andrade|LMA|', 'de Oliveira Faria|Gabriela|G|', 'Isoldi|Mauro César|MC|', 'Castro-Borges|William|W|', 'de Andrade|Milton Hércules Guerra|MHG|']
D000818:Animals D023181:Antimicrobial Cationic Peptides D002352:Carrier Proteins D002478:Cells, Cultured D005347:Fibroblasts D051795:Hypoxia-Inducible Factor 1, alpha Subunit D055767:Immobilized Proteins D008024:Ligands D013058:Mass Spectrometry D024101:Mitochondrial Proteins D016328:NF-kappa B D010446:Peptide Fragments D061988:Proteasome Inhibitors D020543:Proteome D040901:Proteomics D051381:Rats D017208:Rats, Wistar D013552:Swine
PR-11 PR-39 Label-free shotgun PR-11 binding proteins Proline rich-peptides