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Cytoskeletal Breakdown and Apoptosis Elicited by NO Donors in Cerebellar Granule Cells Require NMDA Receptor Activation

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Bonfoco_E_J_Neurochem_1996.pdf
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Datum

1996

Autor:innen

Bonfoco, Emanuela
Zhivotovsky, Boris
Orrenius, Sten
Lipton, Stuart A.
Nicotera, Pieriuigi

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Journal of Neurochemistry. 1996, 67(6), pp. 2484-2493. eISSN 1471-4159. Available under: doi: 10.1046/j.1471-4159.1996.67062484.x

Zusammenfassung

We have recently demonstrated that nitric oxide (NO) donors can trigger either apoptosis or necrosis of neurons as a function of the intensity of the exposure. Here, we show that the apoptosis induced by the NO donors S-nitrosocysteine (SNOC) or S-nitroso-N-acetylpenicillamine (SNAP) in cultured cerebellar granule cells (CGCs) depends on NMDA receptor (NMDA-R) activation leading to intracellular Ca'+ overload. Early dissolution of actin filaments followed by breakdown of microtubUles and nuclear lam ins preceded the appearance of typical apoptotic features. NO donors induced tyrosine nitration in neurons, in a small population of contaminating astrocytes, and in cultures of cerebellar astroglial cells. However, astrocytes neither displayed cytoskeletal alterations nor underwent apoptosis. Competitive and uncompetitive NMDA receptor antagonists, such as Daminophosphonovaleric acid and MK-801, did not influence tyrosine nitration but prevented the accumulation of intracellular Ca", cytoskeletal breakdown, and apoptosis induced by either SNOC or SNAP in CGCs. Taken together, these data strongly suggest that Ca" influx through NMDA-R-gated ion channels is a critical event in CGC apoptosis induced by NO donors.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
540 Chemie

Schlagwörter

Apoptosis, Calcium, Cytoskeleton, Neurodegeneration, Nitric oxide

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ISO 690BONFOCO, Emanuela, Marcel LEIST, Boris ZHIVOTOVSKY, Sten ORRENIUS, Stuart A. LIPTON, Pieriuigi NICOTERA, 1996. Cytoskeletal Breakdown and Apoptosis Elicited by NO Donors in Cerebellar Granule Cells Require NMDA Receptor Activation. In: Journal of Neurochemistry. 1996, 67(6), pp. 2484-2493. eISSN 1471-4159. Available under: doi: 10.1046/j.1471-4159.1996.67062484.x
BibTex
@article{Bonfoco1996Cytos-8149,
  year={1996},
  doi={10.1046/j.1471-4159.1996.67062484.x},
  title={Cytoskeletal Breakdown and Apoptosis Elicited by NO Donors in Cerebellar Granule Cells Require NMDA Receptor Activation},
  number={6},
  volume={67},
  journal={Journal of Neurochemistry},
  pages={2484--2493},
  author={Bonfoco, Emanuela and Leist, Marcel and Zhivotovsky, Boris and Orrenius, Sten and Lipton, Stuart A. and Nicotera, Pieriuigi}
}
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