In vitro cleavage of bioactive peptides by peptidases from Bothrops jararaca venom and its neutralization by bothropic antivenom produced by Butantan Institute: Major contribution of serine peptidases

Author(s)

Kuniyoshi, Alexandre Kazuo ; Kodama, Roberto Tadashi ; Ferreira Moraes, Luis Henrique ; Duzzi, Bruno ; Iwai, Leo Kei ; Lima, Ismael Feitosa ; Cajado-Carvalho, Daniela ; Portaro, Fernanda Vieira

• Document type: Journal article
• Source: Toxicon; v. 137, p. 114-119, OCT 2017.
• Web of Science Citations: 3

Abstract

In Brazil, envenomation by Bothrops pitvipers is responsible for over 73% of snakebites, and their venom is a rich source of proteolytic enzymes. Most studies have demonstrated that Bothrops jararaca venom acts on macromolecular substrates, causing an imbalance in the victim's hemostatic system. In contrast, fewer studies have examined the proteolytic activity on small molecules such as peptides. In this study, we used a set of bioactive peptides (insulin B chain, Met-enkephalin, Leu-enkephalin, neuropeptide Y, peptide YY, pancreatic polypeptide, substance P and somatostatin) to identify new peptide substrates for the metallopeptidases and serine peptidases from the B. jararaca venom. The majority of these peptides were substrates for the venom, but neuropeptide Y and pancreatic polypeptide presented higher hydrolyses rates. Although most of the peptides were simultaneously substrates for both classes of pro teases, serine peptidases were the most active. Substance P was an exclusive substrate for metallopeptidases, while somatostatin was a selective substrate for serine peptidases. The neutralizing efficacy of the bothropic antivenom produced by the Butantan Institute was also assessed and found to totally prevent substance P hydrolysis, whereas somatostatin cleavage was not inhibited. Thus, the antivenom effectively inhibited metallopeptidase activity, but did not neutralize some of the serine peptidases. These results indicate that, in addition to cleaving proteins, the proteolytic enzymes from this venom also hydrolyze bioactive peptides, and this peptidase activity could effectively contribute to some of the many dire manifestations of envenomation. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/13124-5 - Purification and characterization of peptides present in the venom of African snakes: searching for peptidase inhibitor of medical importance
• Grantee: Roberto Tadashi Kodama
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/06677-0 - Study of peptidase activity of the B. jararaca venom and potential neutralizing serum produced at Instituto Butantan upon this activity: new aspects of Bothrops poisoning
• Grantee: Fernanda Calheta Vieira Portaro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/15364-3 - Toxic potential analysis of proteases and peptides present in scorpion Tityus serrulatus venom and the blockage capacity of commercial antivenoms: Enhancing the knowledge of venom and its mechanism of action.
• Grantee: Fernanda Calheta Vieira Portaro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/15344-7 - Efficacy of the bothropic antivenom from Butantan Institute: obtention, characterization and neutralization of serinepeptidases from the venom of Bothrops jararaca
• Grantee: Alexandre Kazuo Kuniyoshi
• Support Opportunities: Scholarships in Brazil - Doctorate