[des-arg(1)]-proctolin: A Novel Nep-like Enzyme Inhibitor Identified In Tityus Serrulatus Venom

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The scorpion Tityus serrulatus venom comprises a complex mixture of molecules that paralyzes and kills preys, especially insects. However, venom components also interact with molecules in humans, causing clinic envenomation. This cross-interaction may result from homologous molecular targets in mammalians and insects, such as (NEP)-like enzymes. In face of these similarities, we searched for peptides in Tityus serrulatus venom using human NEP as a screening tool. We found a NEP-inhibiting peptide with the primary sequence YLPT, which is very similar to that of the insect neuropeptide proctolin (RYLPT). Thus, we named the new peptide [des-Arg(1)]-proctolin. Comparative NEP activity assays using natural substrates demonstrated that [des-Arg(1)]-proctolin has high specificity for NEP and better inhibitory activity than proctolin. To test the initial hypothesis that molecular homologies allow Tityus serrulatus venom to act on both mammal and insect targets, we investigated the presence of a NEP-like in cockroaches, the main scorpion prey, that could be likewise inhibited by [des-Arg(1)]-proctolin. Indeed, we detected a possible NEP-like in a homogenate of cockroach heads whose activity was blocked by thiorphan and also by [des-Arg(1)]-proctolin. Western blot analysis using a human NEP monoclonal antibody suggested a NEP-like enzyme in the homogenate of cockroach heads. Our study describes for the first time a proctolin-like peptide, named [des-Arg(1)]-proctolin, isolated from Tityus serrulatus venom. The tetrapeptide inhibits human NEP activity and a NEP-like activity in a cockroach head homogenate, thus it may play a role in human envenomation as well as in the paralysis and death of scorpion preys. (C) 2015 Elsevier Inc. All rights reserved.801824Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2014/12976-5, 2012/06677-0, 2013/15343-0]Instituto Nacional de Ciencia e Tecnologia em Toxinas-Conselho Nacional de Desenvolvimento Cientifico e TecnologicoConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Erythrocyte Membrane and Renal Function in Relation to Hypertension in Rats of the Milan Hypertensive Strain

1. The aim of this study was to compare certain renal and erythrocyte functions in the Milan hypertensive strain (MHS) of rats and in normotensive control animals (MNS). 2. Under experimental conditions close to those in conscious unmanipulated animals, the glomerular filtration rate (GFR) per g kidney weight was higher and the kidney weight/body weight ratio lower in MHS than in MNS rats (P &amp;lt; 0.001). This suggests that there is increased transtubular ion transport in MHS animals. 3. The MHS rats had a higher rate constant for outward Na+-K+ cotransport than the MNS animals (P &amp;lt; 0.02), their intra-erythrocyte sodium concentrations were lower (P &amp;lt; 0.05) and their erythrocyte volume was smaller (P &amp;lt; 0.001). Therefore, accelerated cell membrane sodium outward cotransport seems to reset the volume and the sodium content of the erythrocytes of MHS rats at a lower level. 4. We speculate that increased transport of ions across the cell membrane may be an abnormality common to erythrocytes and renal tubular cells in MHS rats.</jats:p

Insights into scorpion venom peptides: Alternative processing of beta-KTx propeptide from Tityus serrulatus venom results in a new naturally occurring thimet oligopeptidase inhibitor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Most functions attributed to Tityus serrulatus venom (TsV) are related to active molecules onion-channels; however, here we describe a new pentapeptide that was discovered through enzymatic assay selection using EP24.15. The primary structure analysis revealed the sequence KEXXG (X means Ile or Leu), similar to the sequence present in the beta-KTX propeptide described from the venom of Tityus spp. We confirmed through HPLC analysis that KEILG is the peptide present in TsV, but that KELLG also inhibits EP24.15 although through different mechanisms. (C) 2012 Elsevier Inc. All rights reserved.403033Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)INCTTOXConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq