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

Lade...
Vorschaubild
Dateien
Leist_M_Eur_J_Neurosci_1997.pdf
Leist_M_Eur_J_Neurosci_1997.pdfGröße: 710.79 KBDownloads: 452
Datum
1997
Autor:innen
Fava, Eugenio
Montecucco, Cesare
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Open Access Green
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
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.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
apoptosis, mouse, clostridial neurotoxins, peroxynitrite, NMDA receptor
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690LEIST, 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}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/8264">
    <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>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/8264/1/Leist_M_Eur_J_Neurosci_1997.pdf"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:42:15Z</dcterms:available>
    <dcterms:title>Peroxynitrite and Nitric Oxide Donors Induce Neuronal Apoptosis by Eliciting Autocrine Excitotoxicity</dcterms:title>
    <dc:creator>Nicotera, Pierluigi</dc:creator>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:format>application/pdf</dc:format>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/8264/1/Leist_M_Eur_J_Neurosci_1997.pdf"/>
    <dc:contributor>Nicotera, Pierluigi</dc:contributor>
    <dc:creator>Leist, Marcel</dc:creator>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/8264"/>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <dc:contributor>Fava, Eugenio</dc:contributor>
    <dc:rights>terms-of-use</dc:rights>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:contributor>Leist, Marcel</dc:contributor>
    <dcterms:issued>1997</dcterms:issued>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <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>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Nein
Begutachtet
Diese Publikation teilen