Oligodendrocyte cell death induced by Disialoganglioside GD3

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SIMON, Bernadett, 2000. Oligodendrocyte cell death induced by Disialoganglioside GD3

@phdthesis{Simon2000Oligo-8568, title={Oligodendrocyte cell death induced by Disialoganglioside GD3}, year={2000}, author={Simon, Bernadett}, address={Konstanz}, school={Universität Konstanz} }

2000 application/pdf Simon, Bernadett 2011-03-24T17:44:45Z eng Oligodendrocytes are target of an autoimmune attack in demyelinating diseases. The crucial mediator causing oligodendrocyte loss and myelin degradation has not yet been defined. In order to investigate degeneration of murine oligodendrocytes in vitro, a culture enriched in oligodendrocytes was established. 30 of all cells developed to mature oligodendrocytes, expressing myelin oligodendrocyte glycoprotein. In this culture, no sensitivity of oligodendrocytes to inflammatory cytokines or to stimulation of CD95 was observed. Inhibition of transcription or translation did not sensitise oligodendrocytes for cytokines or CD95-ligation. This result finds correlates and contrary examples in the literature and indicates that these stimuli are not the only ones involved in oligodendrocyte damage in vivo.<br />Althoug ganglioside levels are alterated in demyelination, gangliosides have not been studied before with regard to demyelination. Disialoganglioside GD3, but no structurally similar ganglioside, damaged oligodendrocytes with high cell type specificity. Parallel evaluation of chemically synthesised and bovine brain-derived GD3 ensured the purity of the effect excluding toxcitiy caused by contamination.<br />GD3 induced apoptotic cell death in oligodendrocytes, causing chromatin condensation, phosphatidylserine exposure, cytochrome c release, activation of caspase-3 and maintenance of cellular integrity. The involvement of caspases seemed to be of minor importance in GD3 induced oligodendrocyte death, as their inhibition did not prevent cell death. GD3-caused oligodendrocyte death was inhibited in cells overexpressing human bcl-2. We conclude that mitochondria play an essential role in GD3 triggered apoptosis.<br />That microglia synthesises GD3 in vivo was observed before. This study shows that microglia is able to release GD3 into the culture medium upon activation by inflammatory stimuli. This provides evidence for GD3 as a microglia-derived mediator during inflammation. deposit-license Simon, Bernadett Oligodendrocyte cell death induced by Disialoganglioside GD3 2011-03-24T17:44:45Z Oligodendrozyten-Zelltod induziert durch Disialogangliosid GD3

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

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