Homology modeling, vasorelaxant and bradykinin-potentiating activities of a novel hypotensin found in the scorpion venom from Tityus stigmurus.
In a recent work by our group involving a transcriptomics approach applied to the venom glands from Tityus stigmurus we identified a new family of peptides called Hypotensins (TSTI0006C) (Almeida et al., 2012). The cluster TSTI0006C was analyzed in the main 25 amino acid residues and named T. stigmurus Hypotensin (TistH), showing a molecular mass of 2.7 kDa, an absence of cysteines and the presence of two C-terminal proline residues, which are a bradykinin-potentiating peptide (BPP) signature. Here, we describe the homology modeling of the three-dimensional structure of TistH. In addition, we evaluated the cardiovascular effects elicited by TistH in normotensive rats. Firstly, TistH showed no cytotoxic effect on horse erythrocyte. Furthermore, in normotensive rats TistH was able to potentiate the hypotensive action of bradykinin (BK) and induced a vasorelaxant effect in mesenteric artery rings by endothelium-dependent release of nitric oxide (NO) and demonstrated independent inhibition of angiotensin converting enzyme (ACE). Our data can contribute to a better understanding of the structural and functional characteristics of TistH and suggest its potential use in cardiovascular diseases.
Laboratório de Tecnologia e Biotecnologia Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil; Programa de Pós-Graduação em Bioquímica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
Richele J A
RJ
Machado
Departamento de Biotecnologia da Universidade Federal da Paraíba, João Pessoa, PB, Brazil.
Leônidas G M
LG
Junior
Instituto de Química, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
Norberto K V
NK
Monteiro
Laboratório de Tecnologia e Biotecnologia Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
Arnóbio A
AA
Silva-Júnior
Laboratório de Imunoquímica, Instituto Butantan, São Paulo, SP, Brazil.
Fernanda C V
FC
Portaro
Laboratório de Química Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
Euzébio G
EG
Barbosa
Departamento de Biotecnologia da Universidade Federal da Paraíba, João Pessoa, PB, Brazil.
Valdir A
VA
Braga
Laboratório de Tecnologia e Biotecnologia Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil; Programa de Pós-Graduação em Bioquímica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil. Electronic address: mpedrosa@ufrnet.br.
Matheus F
MF
Fernandes-Pedrosa
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000737:chemistry / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism; D003001:Cloning, Molecular; D019295:Computational Biology; D008958:Models, Molecular; D009569:Nitric Oxide / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000737:chemistry / Q000494:pharmacology*; D012605:Scorpions / Q000378:metabolism*; D059467:Transcriptome; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D012604:Scorpion Venoms; D014665:Vasodilator Agents; D009569:Nitric Oxide; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin
Anti-hypertensive peptides; Bradykinin-potentiating peptides; Hypotensin; Nitric oxide; Tityus stigmurus