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Glutathione intensifies gliotoxin-induced cytotoxicity in human neuroblastoma SH-SY5Y cells
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi.
2006 Inngår i: Cell Biology and Toxicology, Vol. 22, s. 127-136Artikkel i tidsskrift (Fagfellevurdert) Published
sted, utgiver, år, opplag, sider
2006. Vol. 22, s. 127-136
Identifikatorer
URN: urn:nbn:se:su:diva-22977OAI: oai:DiVA.org:su-22977DiVA, id: diva2:189844
Merknad
Part of urn:nbn:se:su:diva-1312Tilgjengelig fra: 2006-10-06 Laget: 2006-10-06bibliografisk kontrollert
Inngår i avhandling
1. Evaluation of neurotoxic properties of gliotoxin
Åpne denne publikasjonen i ny fane eller vindu >>Evaluation of neurotoxic properties of gliotoxin
2006 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The occurrence of mould in food and animal feed is a severe problem due to the secondary metabolites, called mycotoxins, which can possess toxic activity. Aspergillus fumigatus is a common fungus found in improperly stored animal feed and the abundance of spores of the fungus is frequently spread into the air. Gliotoxin has been identified as one of the most toxic second metabolites produced by A. fumigatus. Although A. fumigatus is known to produce mycotoxins that induce neurological syndromes, the neurotoxic properties of gliotoxin have not previously been studied. In this thesis a neurotoxic activity of gliotoxin was demonstrated by using differentiated human neuroblastoma SH-SY5Y cells as a surrogate for the nervous system. The major findings were as follows:

i. Gliotoxin is highly toxic to SH-SY5Y cells and there is a correlation between the toxicity and the cellular redox status.

ii. Gliotoxin reduces the number of neurites, but does not affect the cell bodies morphologically, at non-cytotoxic concentrations. This indicates that the toxin may induce peripheral axonopathy in vivo.

iii. The intracellular free Ca2+ concentration is increased after exposure to gliotoxin, an effect that is the most ubiquitous feature of neuronal cell death. Simultaneously, calpains and caspases, proteases known to be involved in neuronal death and axonal degeneration, are activated.

iv. The observed irreversible neurite degenerative effects of gliotoxin are mainly dependent on caspase activation, whereas calpains are involved in the gliotoxin-induced cytotoxicity.

v. Gliotoxin induces a decreased rate of protein synthesis at non-cytotoxic concentration, which may contribute to the degeneration of neurites.

vi. We did also succeed in developing an in vitro method for determination of toxic activity in animal feed. This study was done in collaboration with National Veterinary Institute (SVA) in Uppsala, and the method is today established and in use at Department of Animal Feed, SVA.

sted, utgiver, år, opplag, sider
Stockholm: Institutionen för neurokemi, 2006. s. 80
Emneord
mycotoxin, gliotoxin, A. fumigatus, cytotoxicity, neurotoxicity
HSV kategori
Identifikatorer
urn:nbn:se:su:diva-1312 (URN)91-7155-286-3 (ISBN)
Disputas
2006-11-17, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 13:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2006-10-06 Laget: 2006-10-06 Sist oppdatert: 2018-01-13bibliografisk kontrollert

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