Title:	A novel vasoactive proline-rich oligopeptide from the skin secretion of the frog Brachycephalus ephippium.
Authors:	ARCANJO, D. D. R. VASCONCELOS, A. G. COMERMA-STEFFENSEN, S. G. JESUS, J. R. SILVA, L. P. da PIRES JÚNIOR, O. R. COSTA-NETO, C. M. OLIVEIRA, E. B. MIGLIOLO, L. FRANCO, O. L. RESTINI, C. B. A. PAULO, M. BENDHACK, L. M. BEMQUERER, M. P. OLIVEIRA, A. P. SIMONSEN, U. LEITE, J. R. de S. de A.
Affiliation:	DANIEL DIAS RUFINO ARCANJO, Universidade Federal do Piauí –UFPI ANDREANNE GOMES VASCONCELOS, Universidade Federal do Piauí –UFPI SIMÓN GABRIEL, Aarhus University JOILSON RAMOS JESUS, Universidade Federal do Piauí –UFPI LUCIANO PAULINO DA SILVA, CENARGEN OSMINDO RODRIGUES PIRES JÚNIOR, Universidade de Brasília–UnB CLAUDIO MIGUEL COSTA-NETO, Universidade de São Paulo–USP, Ribeirão Preto EDUARDO BRANDT OLIVEIRA, Universidade de São Paulo–USP, Ribeirão Preto LUDOVICO MIGLIOLO, Universidade Católica de Brasília–UCB OCTÁVIO LUIZ FRANCO, Universidade Católica de Brasília–UCB CAROLINA BARALDI ARAÚJO RESTINI, Universidade de Ribeirão Preto–UNAERP MICHELE PAULO, Universidade de São Paulo–USP, Ribeirão Preto LUSIANE MARIA BENDHACK, Universidade de São Paulo–USP, Ribeirão Preto MARCELO PORTO BEMQUERER, CENARGEN ALDEIDIA PEREIRA OLIVEIRA, Universidade Federal do Piauí –UFPI ULF SIMONSEN, Aarhus University JOSÉ ROBERTO DE SOUZA DE ALMEIDA LEITE, Universidade Federal do Piauí –UFPI.
Date Issued:	2015
Citation:	Plos One, v. 10, dez. 2015. (Open Access)
Description:	Proline-rich oligopeptides (PROs) are a large family which comprises the bradykinin-potentiating peptides (BPPs). They inhibit the activity of the angiotensin I-converting enzyme (ACE) and have a typical pyroglutamyl (Pyr)/proline-rich structure at the N- and C-terminus, respectively. Furthermore, PROs decrease blood pressure in animals. In the present study, the isolation and biological characterization of a novel vasoactive BPP isolated from the skin secretion of the frog Brachycephalus ephippium is described. This new PRO, termed BPP-Brachy, has the primary structure WPPPKVSP and the amidated form termed BPPBrachyNH2 inhibits efficiently ACE in rat serum. In silico molecular modeling and docking studies suggest that BPP-BrachyNH2 is capable of forming a hydrogen bond network as well as multiple van der Waals interactions with the rat ACE, which blocks the access of the substrate to the C-domain active site. Moreover, in rat thoracic aorta BPP-BrachyNH2 induces potent endothelium-dependent vasodilatation with similar magnitude as captopril. In DAF-FM DA-loaded aortic cross sections examined by confocal microscopy, BPP-BrachyNH2 was found to increase the release of nitric oxide (NO). Moreover, BPP-BrachyNH2 was devoid of toxicity in endothelial and smooth muscle cell cultures. In conclusion, the peptide BPP-BrachyNH2 has a novel sequence being the first BPP isolated from the skin secretion of the Brachycephalidae family. This opens for exploring amphibians as a source of new biomolecules. The BPP-BrachyNH2 is devoid of cytotoxicity and elicits endothelium-dependent vasodilatation mediated by NO. These findings open for the possibility of potential application of these peptides in the treatment of endothelial dysfunction and cardiovascular diseases.
NAL Thesaurus:	secretion
Keywords:	Proline-rich oligopeptides Brachycephalus ephippium
DOI:	10.1371/journal.pone.0145071
Type of Material:	Artigo de periódico
Access:	openAccess
Appears in Collections:	Artigo em periódico indexado (CENARGEN)