Neurotoxic and convulsant effects induced by jack bean ureases on the mammalian nervous system.

Autor: Almeida CGM; Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil; Graduate Program in Medicine and Health Sciences, School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil., Costa-Higuchi K; Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil; Graduate Program in Materials Technology and Engineering, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil., Piovesan AR; Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil; Graduate Program in Celular and Molecular Biology, Center of Biotechnology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Moro CF; Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil; Graduate Program in Medicine and Health Sciences, School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil., Venturin GT; Preclinical Research Center, Brain Institute of Rio Grande do Sul (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil., Greggio S; Preclinical Research Center, Brain Institute of Rio Grande do Sul (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil., Costa-Ferro ZS; Laboratory of Neuroscience, Brain Institute of Rio Grande do Sul (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil., Salamoni SD; Laboratory of Neuroscience, Brain Institute of Rio Grande do Sul (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil., Peigneur S; Laboratory of Toxicology & Pharmacology, University of Leuven (KU Leuven), Leuven, Belgium., Tytgat J; Laboratory of Toxicology & Pharmacology, University of Leuven (KU Leuven), Leuven, Belgium., de Lima ME; Institute of Teaching and Research, Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil., Silva CND; Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Vinadé L; Laboratory of Neurobiology and Toxinology (Lanetox), Universidade Federal do Pampa, São Gabriel, RS, Brazil., Rowan EG; Strathclyde Institute for Biomedical Sciences, University of Strathclyde, Glasgow, UK., DaCosta JC; Laboratory of Neuroscience, Brain Institute of Rio Grande do Sul (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil., Dal Belo CA; Laboratory of Neurobiology and Toxinology (Lanetox), Universidade Federal do Pampa, São Gabriel, RS, Brazil. Electronic address: charistondb@unipampa.br., Carlini CR; Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil; Graduate Program in Medicine and Health Sciences, School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil; Scholl of Medicine, Pontificía Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: celia.carlini@pucrs.br.
Jazyk: angličtina
Zdroj: Toxicology [Toxicology] 2021 Apr 30; Vol. 454, pp. 152737. Date of Electronic Publication: 2021 Feb 22.
DOI: 10.1016/j.tox.2021.152737
Abstrakt: Ureases are microbial virulence factors either because of the enzymatic release of ammonia or due to many other non-enzymatic effects. Here we studied two neurotoxic urease isoforms, Canatoxin (CNTX) and Jack Bean Urease (JBU), produced by the plant Canavalia ensiformis, whose mechanisms of action remain elusive. The neurotoxins provoke convulsions in rodents (LD 50 ∼2 mg/kg) and stimulate exocytosis in cell models, affecting intracellular calcium levels. Here, electrophysiological and brain imaging techniques were applied to elucidate their mode of action. While systemic administration of the toxins causes tonic-clonic seizures in rodents, JBU injected into rat hippocampus induced spike-wave discharges similar to absence-like seizures. JBU reduced the amplitude of compound action potential from mouse sciatic nerve in a tetrodotoxin-insensitive manner. Hippocampal slices from CNTX-injected animals or slices treated in vitro with JBU failed to induce long term potentiation upon tetanic stimulation. Rat cortical synaptosomes treated with JBU released L-glutamate. JBU increased the intracellular calcium levels and spontaneous firing rate in rat hippocampus neurons. MicroPET scans of CNTX-injected rats revealed increased [18] Fluoro-deoxyglucose uptake in epileptogenesis-related areas like hippocampus and thalamus. Curiously, CNTX did not affect voltage-gated sodium, calcium or potassium channels currents, neither did it interfere on cholinergic receptors, suggesting an indirect mode of action that could be related to the ureases' membrane-disturbing properties. Understanding the neurotoxic mode of action of C. ensiformis ureases could help to unveil the so far underappreciated relevance of these toxins in diseases caused by urease-producing microorganisms, in which the human central nervous system is affected.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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