Disialoganglioside GD3 is released by microglia and induces oligodendrocyte apoptosis

Simon, Bernadett; Malisan, Florence; Testi, Roberto; Nicotera, Pierluigi; Leist, Marcel

Disialoganglioside GD3 is released by microglia and induces oligodendrocyte apoptosis

Dateien

Leist_Simon_Disialoganglioside.pdfGröße: 341.59 KBDownloads: 679

Datum

2002

Autor:innen

Simon, Bernadett

Malisan, Florence

Testi, Roberto

Nicotera, Pierluigi

Leist, Marcel

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Cell Death and Differentiation. 2002, 9(7), pp. 758-767. ISSN 1350-9047. Available under: doi: 10.1038/sj.cdd.4401027

Zusammenfassung

Increased brain ganglioside levels are a hallmark of various neuroinflammatory pathologies. Here, we provide evidence that murine microglia can secrete disialoganglioside GD3 upon exposure to inflammatory stimuli. Comparison of different neural cell types revealed a particular and specific sensitivity of oligodendrocytes towards exogenous GD3. Oligodendrocyte death triggered by GD3 was preceded by degeneration of cellular processes, and associated with typical features of apoptosis, such as chromatin condensation, exposure of phosphatidylserine, release of cytochrome c from mitochondria, and loss of mitochondrial membrane potential, followed by the loss of plasma membrane integrity and detachment of disintegrated oligodendrocytes. Overexpression of bcl-2 partially protected oligodendrocytes from death. In contrast, treatment with the pan-caspase inhibitor zVAD-fmk did not prevent phosphatidylserine exposure, chromatin margination at the nuclear periphery, and death, although caspase-3 was blocked. Thus, GD3 produced by microglia under neuroinflammatory conditions may function as a novel mediator triggering mitochondria-mediated, but caspase-independent, apoptosis-like death of oligodendrocytes.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

oligodendrocyte, microglia, apoptosis, ganglioside, mitochondria, demyelination

Zitieren

ISO 690

SIMON, Bernadett, Florence MALISAN, Roberto TESTI, Pierluigi NICOTERA, Marcel LEIST, 2002. Disialoganglioside GD3 is released by microglia and induces oligodendrocyte apoptosis. In: Cell Death and Differentiation. 2002, 9(7), pp. 758-767. ISSN 1350-9047. Available under: doi: 10.1038/sj.cdd.4401027

BibTex

@article{Simon2002-07Disia-20169,
  year={2002},
  doi={10.1038/sj.cdd.4401027},
  title={Disialoganglioside GD3 is released by microglia and induces oligodendrocyte apoptosis},
  number={7},
  volume={9},
  issn={1350-9047},
  journal={Cell Death and Differentiation},
  pages={758--767},
  author={Simon, Bernadett and Malisan, Florence and Testi, Roberto and Nicotera, Pierluigi and Leist, Marcel}
}

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