The fungal neurotoxin penitrem A induces the production of reactive oxygen species in human neutrophils at submicromolar concentrations.
Toxicology
; 392: 64-70, 2017 12 01.
Article
em En
| MEDLINE
| ID: mdl-29037868
ABSTRACT
Penitrem A is a fungal neurotoxin that recurrently causes intoxication in animals, and occasionally also in humans. We have previously reported that penitrem A induced the production of reactive oxygen species (ROS) in rat cerebellar granule cells, opening for a new mechanism of action for the neurotoxin. The aim of this study was to examine the potential of penitrem A to induce ROS production in isolated human neutrophil granulocytes, and to study possible mechanisms involved. Penitrem A significantly increased the production of ROS in human neutrophils at concentrations as low as 0.25µM (40% increase over basal levels), as measured with the DCF fluorescence assay. The EC50 determined for the production of ROS by penitrem A was 3.8µM. The maximal increase in ROS production was approximately 330% over basal levels at a concentration of 12.5µM. ROS formation was significantly inhibited by the antioxidant vitamin E (50µM), the intracellular Ca+2 chelator BAPTA-AM (5µM), the mitogen activated protein kinase kinase (MEK) 1/2 and 5 inhibitor U0126 (1 and 10µM), the p38 mitogen activated protein kinase (MAPK) inhibitor SB203580 (1µM), the c-Jun amino-terminal kinase (JNK) inhibitor SP600125 (10µM), and the calcineurin inhibitors FK-506 and cyclosporine A (1.5 and 0.5µM, respectively). These finding suggest that penitrem A is able to induce an increase in ROS production in neutrophils via the activation of several MAPK-signalling pathways. We suggest that this increase may partly explain the pathophysiology generated by penitrem A neuromycotoxicosis in both humans and animals.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espécies Reativas de Oxigênio
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Micotoxinas
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Neurotoxinas
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Neutrófilos
Limite:
Humans
Idioma:
En
Revista:
Toxicology
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Noruega