@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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    <dc:contributor>Montecucco, Cesare</dc:contributor>
    <dcterms:abstract xml:lang="eng">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.</dcterms:abstract>
    <dc:creator>Fava, Eugenio</dc:creator>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:42:15Z</dc:date>
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    <dcterms:title>Peroxynitrite and Nitric Oxide Donors Induce Neuronal Apoptosis by Eliciting Autocrine Excitotoxicity</dcterms:title>
    <dc:creator>Nicotera, Pierluigi</dc:creator>
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    <dc:contributor>Nicotera, Pierluigi</dc:contributor>
    <dc:creator>Leist, Marcel</dc:creator>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/8264"/>
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    <dc:contributor>Fava, Eugenio</dc:contributor>
    <dc:rights>terms-of-use</dc:rights>
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    <dc:contributor>Leist, Marcel</dc:contributor>
    <dcterms:issued>1997</dcterms:issued>
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    <dcterms:bibliographicCitation>First publ. in: European Journal of Neuroscience ; 9 (1997), 7. - pp. 1488-1498</dcterms:bibliographicCitation>
    <dc:language>eng</dc:language>
    <dc:creator>Montecucco, Cesare</dc:creator>
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