| Registro completo |
| Provedor de dados: |
Repositório Alice
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| País: |
Brazil
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| Título: |
A novel vasoactive proline-rich oligopeptide from the skin secretion of the frog Brachycephalus ephippium.
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| Autores: |
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.
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| Data: |
2015-12-15
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| Ano: |
2015
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| Palavras-chave: |
Proline-rich oligopeptides
Brachycephalus ephippium
Secretion
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| Resumo: |
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.
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| Tipo: |
Separatas
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| Idioma: |
Inglês
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| Identificador: |
Plos One, v. 10, dez. 2015. (Open Access)
http://www.alice.cnptia.embrapa.br/alice/handle/doc/1031700
10.1371/journal.pone.0145071
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| Direitos: |
openAccess
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