A novel vasoactive proline-rich oligopeptide from the skin secretion of the frog Brachycephalus ephippium.

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.

Bibliographic Details

Main 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.
Other Authors:	DANIEL DIAS RUFINO ARCANJO, Universidade Federal do Piauí –UFPI
Format:	Separatas biblioteca
Language:	English eng
Published:	2015-12-15
Subjects:	Proline-rich oligopeptides, Brachycephalus ephippium, secretion,
Online Access:	http://www.alice.cnptia.embrapa.br/alice/handle/doc/1031700
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