Neuropeptide Y Family-Degrading Metallopeptidases in the Tityus serrulatus Venom Partially Blocked by Commercial Antivenoms

Autor(es)

Carvalho, Daniela Cajado ^[1] ; Kuniyoshi, Alexandre K. ^[1] ; Kodama, Roberto T. ^[1] ; Oliveira, Ana K. ^[2] ; Serrano, Solange M. T. ^[2] ; Tambourgi, Denise V. ^[1] ; Portaro, Fernanda V. ^[1]

Afiliação do(s) autor(es)

^[1] Butantan Inst, Immunochem Lab, BR-05503900 Sao Paulo - Brazil

^[2] Butantan Inst, Special Lab Appl Toxinol, Ctr Toxins Immune Response & Cell Signaling CeTIC, BR-05503900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: TOXICOLOGICAL SCIENCES; v. 142, n. 2, p. 418-426, DEC 2014.
• Citações Web of Science: 5

Resumo

Accidents caused by scorpions represent a relevant public health issue in Brazil, being more recurring than incidents with snakes and spiders. The main species responsible for this situation is the yellow scorpion, Tityus serrulatus, due especially to the great frequency with which accidents occur and the potential of its venom to induce severe clinical manifestations, even death, mainly among children. Although neurotoxins are well characterized, little information is known about other components of scorpion venoms, such as peptidases, and their effect on envenomation. Previous results from our group showed that the metallopeptidases present in this venom are capable of hydrolyzing the neuropeptide dynorphin 1-13 in vitro, releasing Leu-enkephalin, which may interact with ion channels and promote indirect neurotoxicity. Thus, this study aims to get more information about the effect of toxic peptidase activity present in the venom on biologically active peptides, and to evaluate the in vitro neutralizing potential of commercial antivenoms produced by the Butantan Institute. A set of human bioactive peptides were studied as substrates for the peptidases, and the members of the neuropeptide Y family were found to be the most susceptible ones. All new substrate hydrolyses were totally inhibited by ethylenediaminetetracetic and not blocked by phenylmethanesulfonylfluoride, indicating that metallopeptidases were responsible for the peptidase activity. Also, peptidase activities were only partially inhibited by therapeutic Brazilian scorpion antivenom (SAV) and arachnid antivenom (AAV). The dose-response inhibition by both antivenoms indicates that AAV neutralizes better than SAV at the used doses. These characterizations, unpublished until now, can contribute to the improvement of our knowledge about the venom and envenomation processes by T. serrulatus. (AU)

• 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: 13/15343-0 - Purificação e caracterização de peptidases presentes no veneno do escorpião Tityus serrulatus
• Beneficiário: Daniela Cajado de Oliveira Souza Carvalho
• Modalidade de apoio: Bolsas no Brasil - Doutorado