Peroxynitrite and Nitric Oxide Donors Induce Neuronal Apoptosis by Eliciting Autocrine Excitotoxicity

Leist, Marcel; Fava, Eugenio; Montecucco, Cesare; Nicotera, Pierluigi

Peroxynitrite and Nitric Oxide Donors Induce Neuronal Apoptosis by Eliciting Autocrine Excitotoxicity

Dateien

Leist_M_Eur_J_Neurosci_1997.pdfGröße: 710.79 KBDownloads: 444

Datum

1997

Autor:innen

Leist, Marcel

Fava, Eugenio

Montecucco, Cesare

Nicotera, Pierluigi

Publikationstyp

Zeitschriftenartikel

unikn.publication.listelement.citation.prefix.version.undefined

European Journal of Neuroscience. 1997, 9(7), pp. 1488-1498. ISSN 0953-816X. eISSN 1460-9568. Available under: doi: 10.1111/j.1460-9568.1997.tb01503.x

Zusammenfassung

Endogenous generation of nitric oxide and its congeners, including peroxynitrite (ONOO-), has been implicated in the mechanism of neuron loss in neurodegenerative diseases. Accordingly, nitric oxide donors and ONOO-can elicit both apoptosis and necrosis in neuron cultures. Here we show that nitric oxide donors and ONOO- are each able to trigger apoptosis of mouse cerebellar granule cells by an excitotoxic mechanism requiring exocytosis and NMDA receptor-mediated intracellular Ca2+ overload. This conclusion is supported by the following findings. Apoptosis was induced by various nitric oxide donors or by direct addition of ONOO- to differentiated cerebellar granule cell cultures that were sensitive to NMDA toxicity, but not in cerebellar granule cells that did not display NMDA-induced cell death (i.e. early days in culture) or in various glial cell populations. Donors of ONOO- or nitric oxide stimulated a sustained increase in intracellular Ca2+, which was prevented by inhibitors of NMDA receptors, such as MK-801 and 5-phospho-aminovaleric acid, or by dampening neuronal electrical activity with high concentrations of extracellular Mg2+. Moreover, these treatments and the exposure of cerebellar granule cells in nominally Ca2+-free media prevented apoptotic cell death. Both the intracellular Ca2+ increase and apoptosis elicited by ONOO- or the nitric oxide donors were prevented by blocking exocytosis with tetanus toxin or botulinum neurotoxin C.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

apoptosis, mouse, clostridial neurotoxins, peroxynitrite, NMDA receptor

Zitieren

ISO 690

LEIST, Marcel, Eugenio FAVA, Cesare MONTECUCCO, Pierluigi NICOTERA, 1997. Peroxynitrite and Nitric Oxide Donors Induce Neuronal Apoptosis by Eliciting Autocrine Excitotoxicity. In: European Journal of Neuroscience. 1997, 9(7), pp. 1488-1498. ISSN 0953-816X. eISSN 1460-9568. Available under: doi: 10.1111/j.1460-9568.1997.tb01503.x

BibTex

@article{Leist1997Perox-8264,
  year={1997},
  doi={10.1111/j.1460-9568.1997.tb01503.x},
  title={Peroxynitrite and Nitric Oxide Donors Induce Neuronal Apoptosis by Eliciting Autocrine Excitotoxicity},
  number={7},
  volume={9},
  issn={0953-816X},
  journal={European Journal of Neuroscience},
  pages={1488--1498},
  author={Leist, Marcel and Fava, Eugenio and Montecucco, Cesare and Nicotera, Pierluigi}
}

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