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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 9
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: Biochimie; v. 115, p. 8-16, AUG 2015.
Web of Science Citations: 12
Abstract

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)

FAPESP's process: 13/26200-6 - Venomics plataform of Pachycondyla villosa proteome, transcriptome, cloning and expression of toxins with biotechnological potential
Grantee:Camila Takeno Cologna
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 13/21329-0 - Electrophysiological characterization of Tityus serrulatus venom toxins Ts3, Ts4, Ts6, Ts8, Ts15 and TS venom peptide 7: looking for new desired drugs
Grantee:Manuela Berto Pucca
Support type: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 09/07169-5 - Lipid mediators as regulators of immune response
Grantee:Lúcia Helena Faccioli
Support type: Research Projects - Thematic Grants
FAPESP's process: 14/03332-7 - Study of the relationship between inflammasome activation and lipid mediators production with pulmonary inflammation induced by scorpion venom with and without hyaluronidase
Grantee:Karina Furlani Zoccal
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 13/21342-7 - Electrophysiological characterization of Ts19 fragment II, a new toxin purified from Tityus serrulatus venom
Grantee:Felipe Augusto Cerni
Support type: Scholarships abroad - Research Internship - Doctorate