Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 137, p. 114-119, OCT 2017.
• Citações Web of Science: 3

Resumo

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)

• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 15/13124-5 - Purificação e caracterização de peptídeos presentes nos venenos de serpentes africanas: à procura de inibidores de peptidases de importância médica
• Beneficiário: Roberto Tadashi Kodama
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/06677-0 - Estudo da atividade peptidásica dos venenos botrópicos e do potencial neutralizante do soro produzido no Instituto Butantan sobre esta atividade: novos aspectos sobre o envenenamento botrópico
• Beneficiário: Fernanda Calheta Vieira Portaro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/15364-3 - Análise do potencial tóxico de proteases e peptídeos presentes no veneno do escorpião Tityus serrulatus e do poder neutralizante dos antivenenos comerciais: Aprimorando o conhecimento do veneno e seu mecanismo de ação.
• Beneficiário: Fernanda Calheta Vieira Portaro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/15344-7 - Eficácia do soro antibotrópico produzido no Instituto Butantan: obtenção, caracterização e neutralização de serinopeptidases de interesse do veneno de Bothrops jararaca
• Beneficiário: Alexandre Kazuo Kuniyoshi
• Modalidade de apoio: Bolsas no Brasil - Doutorado