PMID- 25930987 OWN - NLM STAT- MEDLINE DCOM- 20160325 LR - 20220408 IS - 1879-3150 (Electronic) IS - 0041-0101 (Linking) VI - 101 DP - 2015 Jul TI - Homology modeling, vasorelaxant and bradykinin-potentiating activities of a novel hypotensin found in the scorpion venom from Tityus stigmurus. PG - 11-8 LID - S0041-0101(15)00100-2 [pii] LID - 10.1016/j.toxicon.2015.04.003 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Machado, Richele J A AU - Machado RJ AD - Laboratorio de Tecnologia e Biotecnologia Farmaceutica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil; Programa de Pos-Graduacao em Bioquimica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil. FAU - Junior, Leonidas G M AU - Junior LG AD - Departamento de Biotecnologia da Universidade Federal da Paraiba, Joao Pessoa, PB, Brazil. FAU - Monteiro, Norberto K V AU - Monteiro NK AD - Instituto de Quimica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil. FAU - Silva-Junior, Arnobio A AU - Silva-Junior AA AD - Laboratorio de Tecnologia e Biotecnologia Farmaceutica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil. FAU - Portaro, Fernanda C V AU - Portaro FC AD - Laboratorio de Imunoquimica, Instituto Butantan, Sao Paulo, SP, Brazil. FAU - Barbosa, Euzebio G AU - Barbosa EG AD - Laboratorio de Quimica Farmaceutica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil. FAU - Braga, Valdir A AU - Braga VA AD - Departamento de Biotecnologia da Universidade Federal da Paraiba, Joao Pessoa, PB, Brazil. FAU - Fernandes-Pedrosa, Matheus F AU - Fernandes-Pedrosa MF AD - Laboratorio de Tecnologia e Biotecnologia Farmaceutica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil; Programa de Pos-Graduacao em Bioquimica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil. Electronic address: mpedrosa@ufrnet.br. LA - eng PT - Journal Article DEP - 20150428 PL - England TA - Toxicon JT - Toxicon : official journal of the International Society on Toxinology JID - 1307333 RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Antihypertensive Agents) RN - 0 (Scorpion Venoms) RN - 0 (Vasodilator Agents) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 3.4.15.1 (Peptidyl-Dipeptidase A) RN - S8TIM42R2W (Bradykinin) SB - IM MH - Angiotensin-Converting Enzyme Inhibitors/chemistry/pharmacology MH - Animals MH - Antihypertensive Agents/pharmacology MH - Blood Pressure/drug effects MH - Bradykinin/chemistry/*pharmacology MH - Cardiovascular System/drug effects/metabolism MH - Cloning, Molecular MH - Computational Biology MH - Models, Molecular MH - Nitric Oxide/metabolism MH - Peptidyl-Dipeptidase A/metabolism MH - Rats MH - Rats, Wistar MH - Scorpion Venoms/chemistry/*pharmacology MH - Scorpions/*metabolism MH - Transcriptome MH - Vasodilator Agents/chemistry/*pharmacology OTO - NOTNLM OT - Anti-hypertensive peptides OT - Bradykinin-potentiating peptides OT - Hypotensin OT - Nitric oxide OT - Tityus stigmurus EDAT- 2015/05/02 06:00 MHDA- 2016/03/26 06:00 CRDT- 2015/05/02 06:00 PHST- 2014/12/08 00:00 [received] PHST- 2015/03/18 00:00 [revised] PHST- 2015/04/21 00:00 [accepted] PHST- 2015/05/02 06:00 [entrez] PHST- 2015/05/02 06:00 [pubmed] PHST- 2016/03/26 06:00 [medline] AID - S0041-0101(15)00100-2 [pii] AID - 10.1016/j.toxicon.2015.04.003 [doi] PST - ppublish SO - Toxicon. 2015 Jul;101:11-8. doi: 10.1016/j.toxicon.2015.04.003. Epub 2015 Apr 28.