Machado Richele J A, Junior Leônidas G M, Monteiro Norberto K V, Silva-Júnior Arnóbio A, Portaro Fernanda C V, Barbosa Euzébio G, Braga Valdir A, Fernandes-Pedrosa Matheus F
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.
Departamento de Biotecnologia da Universidade Federal da Paraíba, João Pessoa, PB, Brazil.
Toxicon. 2015 Jul;101:11-8. doi: 10.1016/j.toxicon.2015.04.003. Epub 2015 Apr 28.
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.
在我们小组最近的一项工作中，采用转录组学方法研究了巴西金幽灵蝎（Tityus stigmurus）的毒腺，我们鉴定出了一个名为降血压肽（Hypotensins，TSTI0006C）的新肽家族（阿尔梅达等人，2012年）。对TSTI0006C簇中的主要25个氨基酸残基进行了分析，并将其命名为巴西金幽灵蝎降血压肽（TistH），其分子量为2.7 kDa，不含半胱氨酸，且有两个C端脯氨酸残基，这是一种缓激肽增强肽（BPP）的特征。在此，我们描述了TistH三维结构的同源性建模。此外，我们评估了TistH对正常血压大鼠的心血管效应。首先，TistH对马红细胞没有细胞毒性作用。此外，在正常血压大鼠中，TistH能够增强缓激肽（BK）的降压作用，并通过内皮依赖性释放一氧化氮（NO）在肠系膜动脉环中诱导血管舒张作用，还表现出对血管紧张素转换酶（ACE）的独立抑制作用。我们的数据有助于更好地理解TistH的结构和功能特性，并表明其在心血管疾病中的潜在应用价值。
