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New functional perspectives of a serine protease from Crotalus durissus collilineatus: activity on voltage-gated ion channels

Grant number: 15/16714-8
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): March 01, 2016
Effective date (End): December 16, 2016
Field of knowledge:Health Sciences - Pharmacy - Toxicological Analysis
Principal researcher:Eliane Candiani Arantes Braga
Grantee:Johara Boldrini França
Supervisor abroad: Jan Tytgat
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: University of Leuven (KU Leuven), Belgium  
Associated to the scholarship:14/16182-3 - New functional perspectives of a serine protease from Crotalus durissus collilineatus: activity on voltage-gated ion channels, BP.PD

Abstract

The complexity and variety of physiological targets in which snake venom toxins interact make them important candidates as models in the development of new drugs and biological tools. The venoms from Viperidae snakes are rich sources of proteolytic enzymes that exert various biological activities in the prey or victim, such as activation of the complement system and inflammation, changes in cell differentiation, influences in hemostatic system, among others. Snake venom serine proteases (SVSPs) act mainly on plasma proteins, generating a variety of physiological changes with effects on platelet aggregation, blood coagulation, fibrinolysis, blood pressure, complement system and nervous system. However, the complexity of the mechanisms by which SVSPs affect the homeostasis of the victim was not yet completely clarified. Therefore, this project aims to find new perspectives on the functionality of a SVSP from Crotalus durissus collilineatus, named collinein-1, in order to expand the fields of application of this class of toxins. In this context, we propose to investigate the action of collinein-1 in native, recombinant and mutant (enzymatically inactive by presenting a substitution in His43 by Arg43 in the catalytic triad) forms on different voltage-gated ion channels, since rCollinein-1 was able to specifically block Kv10.1 channels in a previous electrophysiological screening. Toxins will be tested for their effect on various voltage-gated ion channels (Kv and Nav) expressed in Xenopus laevis oocytes by electrophysiology assays. The effects of collinein-1 on the voltage-gated ion channel on which it is active will be investigated by electrophysiological characterization, including the determination of the concentration-response curve and IC50, analysis of the reversibility of the activity and determination of the current-voltage curve of the enzymes on the ion channel. Ionic channels play important cellular functions such as excitation of nerves and muscle cells, regulation of blood pressure, mobility and sperm capacitation and modulation of tumor cell proliferation. Despite the importance of these channels, there are few snake toxins that was already studied for their action on ion channels, which reinforces the importance of the proposed study in the search for new ion channel modulating or blocking toxins with potential application in various areas of science and/or health. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BOLDRINI-FRANCA, JOHARA; COLOGNA, CAMILA TAKENO; PUCCA, MANUELA BERTO; FIGUEIREDO BORDON, KARLA DE CASTRO; AMORIM, FERNANDO GOBBI; PINO ANJOLETTE, FERNANDO ANTONIO; CORDEIRO, FRANCIELLE ALMEIDA; WIEZEL, GISELE ADRIANO; CERNI, FELIPE AUGUSTO; PINHEIRO-JUNIOR, ERNESTO LOPES; et al. Minor snake venom proteins: Structure, function and potential applications. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1861, n. 4, p. 824-838, . (14/06170-8, 11/12317-3, 11/23236-4, 15/16714-8, 12/13590-8, 13/26619-7, 14/15644-3, 12/12954-6, 13/26200-6)
BOLDRINI-FRANCA, JOHARA; PINHEIRO-JUNIOR, ERNESTO LOPES; PEIGNEUR, STEVE; PUCCA, MANUELA BERTO; CERNI, FELIPE AUGUSTO; BORGES, RAFAEL JUNQUEIRA; COSTA, TASSIA RAFAELLA; IMAI CARONE, SANTE EMMANUEL; DE MATTOS FONTES, MARCOS ROBERTO; SAMPAIO, SUELY VILELA; et al. Beyond hemostasis: a snake venom serine protease with potassium channel blocking and potential antitumor activities. SCIENTIFIC REPORTS, v. 10, n. 1, . (15/16714-8, 16/24191-8, 16/04761-4, 14/16182-3, 15/00740-0, 15/17286-0, 15/18432-0, 17/13485-3, 17/14035-1, 18/14158-9, 11/23236-4)

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