dc.contributor.author | Berntsen, Hanne Friis | |
dc.contributor.author | Bogen, Inger Lise | |
dc.contributor.author | Wigestrand, Mattis B | |
dc.contributor.author | Fonnum, Frode | |
dc.contributor.author | Walaas, S. Ivar | |
dc.contributor.author | Moldes-Anaya, Angel | |
dc.date.accessioned | 2024-08-30T07:57:41Z | |
dc.date.available | 2024-08-30T07:57:41Z | |
dc.date.created | 2017-10-19T16:08:14Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Toxicology. 2017, 392 64-70. | |
dc.identifier.issn | 0300-483X | |
dc.identifier.uri | https://hdl.handle.net/11250/3149223 | |
dc.description.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 0.25 μM (40% increase over basal levels), as measured with the DCF fluorescence assay. The EC50 determined for the production of ROS by penitrem A was 3.8 μM. The maximal increase in ROS production was approximately 330% over basal levels at a concentration of 12.5 μM. ROS formation was significantly inhibited by the antioxidant vitamin E (50 μM), the intracellular Ca+2 chelator BAPTA-AM (5 μM), the mitogen activated protein kinase kinase (MEK) 1/2 and 5 inhibitor U0126 (1 and 10 μM), the p38 mitogen activated protein kinase (MAPK) inhibitor SB203580 (1 μM), the c-Jun amino-terminal kinase (JNK) inhibitor SP600125 (10 μM), and the calcineurin inhibitors FK-506 and cyclosporine A (1.5 and 0.5 μM, 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. | |
dc.description.abstract | The fungal neurotoxin penitrem A induces the production of reactive oxygen species in human neutrophils at submicromolar concentrations | |
dc.language.iso | eng | |
dc.title | The fungal neurotoxin penitrem A induces the production of reactive oxygen species in human neutrophils at submicromolar concentrations | |
dc.title.alternative | The fungal neurotoxin penitrem A induces the production of reactive oxygen species in human neutrophils at submicromolar concentrations | |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.description.version | publishedVersion | |
dc.source.pagenumber | 64-70 | |
dc.source.volume | 392 | |
dc.source.journal | Toxicology | |
dc.identifier.doi | 10.1016/j.tox.2017.10.008 | |
dc.identifier.cristin | 1506038 | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |