Biological characterization of crotoxin and its basic subunit in the neuromuscular junction: radiochemical and real-time video-microscopy studies

• Grant number: 13/03624-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: July 10, 2013
• End date: March 09, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Marcos Roberto de Mattos Fontes
• Grantee: Walter Luís Garrido Cavalcante
• Supervisor: Paulo Jorge Silva Correia Sá
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: Universidade do Porto (UP), Portugal
• Associated to the scholarship: 12/00428-8 - Structural and Functional Characterization of Crotoxin and its Basic Subunit in the Neuromuscular Junction and Influence of Neutralizing Agents, BP.PD

Abstract

The crotoxin is the main toxic fraction present in the venom of Crotalus durissus terrificus. This protein is a heterodimeric complex consisting of a basic phospholipase A2 (PLA2), crotoxin B (CB), associated with a chaperon and nonenzymatic subunit, crotapotin (CA). Pharmacological studies have revealed that the neuromuscular junction is a important site of action of this toxin, which causes muscle paralysis due to a sum of pre and postsynaptic effects. Unfortunately, despite the efforts devoted to this subject, the mechanism of action and the molecular site of action of crotoxin are unknown. Thus, the aim of this project is investigate the kinetics of neurotransmitter released under the influence of crotoxin or CB, through the quantification of evoked [3H]-acetylcholine release and evaluation of real time exocytosis of chemical mediator. Together, this study will advance in the knowledge of the pre-synaptic action of crotoxin. (AU)

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)

CAVALCANTE, WALTER L. G.; NORONHA-MATOS, JOSE B.; TIMOTEO, MARIA A.; FONTES, MARCOS R. M.; GALLACCI, MARCIA; CORREIA-DE-SA, PAULO. Neuromuscular paralysis by the basic phospholipase A(2) subunit of crotoxin from Crotalus durissus terrificus snake venom needs its acid chaperone to concurrently inhibit acetylcholine release and produce muscle blockage. Toxicology and Applied Pharmacology, v. 334, p. 8-17, NOV 1 2017. (13/17864-8, 13/03624-5, 12/00428-8)