Electrophysiological characterization of the first Tityus serrulatus alpha-like toxin, Ts5: Evidence of a pro-inflammatory toxin on macrophages

Autor(es)

Pucca, Manuela B. ^[1] ; Peigneur, Steve ^[2] ; Cologna, Camila T. ^[1] ; Cerni, Felipe A. ^[1] ; Zoccal, Karina F. ^[3] ; Bordon, Karla de C. F. ^[1] ; Faccioli, Lucia H. ^[3] ; Tytgat, Jan ^[2] ; Arantes, Eliane C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Katholieke Univ Leuven, Toxicol & Pharmacol, Leuven - Belgium

^[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal, BR-14040903 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Biochimie; v. 115, p. 8-16, AUG 2015.
• Citações Web of Science: 12

Resumo

Tityus serrulatus (Ts) venom is composed of mainly neurotoxins specific for voltage-gated K+ and Na+ channels, which are expressed in many cells such as macrophages. Macrophages are the first line of defense invasion and they participate in the inflammatory response of Ts envenoming. However, little is known about the effect of Ts toxins on macrophage activation. This study investigated the effect of Ts5 toxin on different sodium channels as well as its role on the macrophage immunomodulation. The electrophysiological assays showed that Ts5 inhibits the rapid inactivation of the mammalian sodium channels Nav1.2, Nav1.3, Nav1A, Nav1.5, Nav1.6 and Nav1.7. Interestingly, Ts5 also inhibits the inactivation of the insect Drosophila melanogaster sodium channel (DmNav1), and it is therefore classified as the first Ts a-like toxin. The immunological experiments on macrophages reveal that Ts5 is a proinflammatory toxin inducing the cytokine production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. On the basis of recent literature, our study also stresses a possible mechanism responsible for venom-associated molecular patterns (VAMPS) internalization and macrophage activation and moreover we suggest two main pathways of VAMPs signaling: direct and indirect. This work provides useful insights for a better understanding of the involvement of VAMPs in macrophage modulation. (C) 2015 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved. (AU)

• Processo FAPESP: 13/21342-7 - Caracterização eletrofisiológica da Ts19 fragmento II, uma nova toxina purificada da peçonha de Tityus serrulatus
• Beneficiário: Felipe Augusto Cerni
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 14/03332-7 - Estudo da relação entre ativação do inflamassoma e produção de mediadores lipídicos com a inflamação pulmonar induzida por veneno de escorpião com e sem hialuronidase
• Beneficiário: Karina Furlani Zoccal
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/21329-0 - Caracterização eletrofisiológica das toxinas provenientes da peçonha de Tityus serrulatus Ts3, Ts4, Ts6, Ts8, Ts15 e TS venom peptide 7: busca de novas drogas terapêuticas
• Beneficiário: Manuela Berto Pucca
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 09/07169-5 - Mediadores lipídicos como reguladores da resposta imune
• Beneficiário: Lúcia Helena Faccioli
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/26200-6 - Plataforma Venômica: Proteoma, Transcriptoma, Clonagem e Expressão de toxinas de interesse biotecnológico presentes na peçonha de Pachycondyla villosa
• Beneficiário: Camila Takeno Cologna
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado