Insights into the Hypertensive Effects of Tityus serrulatus Scorpion Venom: Purification of an Angiotensin-Converting Enzyme-Like Peptidase

• Published in: Toxins Vol. 8; no. 12; p. 348
• Main Authors: Cajado-Carvalho, Daniela, Kuniyoshi, Alexandre Kazuo, Duzzi, Bruno, Iwai, Leo Kei, Oliveira, Úrsula Castro de, Junqueira de Azevedo, Inácio de Loiola Meirelles, Kodama, Roberto Tadashi, Portaro, Fernanda Vieira
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24-11-2016; MDPI
• Subjects: ACE-like; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Antivenins - pharmacology; antivenom; Bioinformatics; Captopril - pharmacology; Chlorides - pharmacology; Hypertension; Hypertension - metabolism; Neurotoxins; Neutralization; Peptide Hydrolases - metabolism; Peptidyl-Dipeptidase A - metabolism; proteases; Scorpion Venoms - pharmacology; Scorpions; Tityus; Tityus serrulatus; Tityus serrulatus venom; ACE-like; Tityus serrulatus venom; hypertension; antivenom; proteases
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins8120348

The number of cases of envenomation by scorpions has grown significantly in Brazil since 2007, with the most severe cases being caused by the
scorpion. Although envenomed patients mostly suffer neurotoxic manifestations, other symptoms, such as hypertension, cannot be exclusively attributed to neurotoxins. Omics analyses have detected plentiful amounts of metalloproteases in
venom. However, the roles played by these enzymes in envenomation are still unclear. Endeavoring to investigate the functions of scorpion venom proteases, we describe here for the first time an Angiotensin I-Converting Enzyme-like peptidase (ACE-like) purified from
venom. The crude venom cleaved natural and fluorescent substrates and these activities were inhibited by captopril. Regarding the serum neutralization, the scorpion antivenom was more effective at blocking the ACE-like activity than arachnid antivenom, although neither completely inhibited the venom cleavage action, even at higher doses. ACE-like was purified from the venom after three chromatographic steps and its identity was confirmed by mass spectrometric and transcriptomic analyses. Bioinformatics analysis showed homology between the ACE-like transcript sequences from
spp. and human testis ACE. These findings advance our understanding of
venom components and may improve treatment of envenomation victims, as ACE-like may contribute to envenomation symptoms, especially the resulting hypertension.