Neuroprotection by Minocycline Caused by Direct and Specific Scavenging of Peroxynitrite

Lade...
Vorschaubild
Dateien
Zu diesem Dokument gibt es keine Dateien.
Datum
2011
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
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Journal of Biological Chemistry. 2011, 286(7), pp. 4991-5002. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1074/jbc.M110.169565
Zusammenfassung

Minocycline prevents oxidative protein modifications and damage in disease models associated with inflammatory glial activation and oxidative stress. Although the drug has been assumed to act by preventing the up-regulation of proinflammatory enzymes, we probed here its direct chemical interaction with reactive oxygen species. The antibiotic did not react with superoxide or •NO radicals, but peroxynitrite (PON) was scavenged in the range of ∼1 μm minocycline and below. The interaction of pharmacologically relevant minocycline concentrations with PON was corroborated in several assay systems and significantly exceeded the efficacy of other antibiotics. Minocycline was degraded during the reaction with PON, and the resultant products lacked antioxidant properties. The antioxidant activity of minocycline extended to cellular systems, because it prevented neuronal mitochondrial DNA damage and glutathione depletion. Maintenance of neuronal viability under PON stress was shown to be solely dependent on direct chemical scavenging by minocycline. We chose α-synuclein (ASYN), known from Parkinsonian pathology as a biologically relevant target in chemical and cellular nitration reactions. Submicromolar concentrations of minocycline prevented tyrosine nitration of ASYN by PON. Mass spectrometric analysis revealed that minocycline impeded nitrations more effectively than methionine oxidations and dimerizations of ASYN, which are secondary reactions under PON stress. Thus, PON scavenging at low concentrations is a novel feature of minocycline and may help to explain its pharmacological activity.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Inflammation, Neurodegeneration, Nitric Oxide, Oxidative Stress, Oxygen Radicals, Parkinson Disease, Synuclein
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690SCHILDKNECHT, Stefan, Regina PAPE, Nathalie MÜLLER, Marta ROBOTTA, Andreas MARQUARDT, Alexander BÜRKLE, Malte DRESCHER, Marcel LEIST, 2011. Neuroprotection by Minocycline Caused by Direct and Specific Scavenging of Peroxynitrite. In: Journal of Biological Chemistry. 2011, 286(7), pp. 4991-5002. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1074/jbc.M110.169565
BibTex
@article{Schildknecht2011-02-18Neuro-13542,
  year={2011},
  doi={10.1074/jbc.M110.169565},
  title={Neuroprotection by Minocycline Caused by Direct and Specific Scavenging of Peroxynitrite},
  number={7},
  volume={286},
  issn={0021-9258},
  journal={Journal of Biological Chemistry},
  pages={4991--5002},
  author={Schildknecht, Stefan and Pape, Regina and Müller, Nathalie and Robotta, Marta and Marquardt, Andreas and Bürkle, Alexander and Drescher, Malte and Leist, Marcel}
}
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/123456789/13542">
    <dc:language>eng</dc:language>
    <dc:contributor>Pape, Regina</dc:contributor>
    <dc:creator>Bürkle, Alexander</dc:creator>
    <dc:creator>Marquardt, Andreas</dc:creator>
    <dc:contributor>Schildknecht, Stefan</dc:contributor>
    <dc:contributor>Marquardt, Andreas</dc:contributor>
    <dc:contributor>Bürkle, Alexander</dc:contributor>
    <dc:creator>Drescher, Malte</dc:creator>
    <dc:contributor>Müller, Nathalie</dc:contributor>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dcterms:title>Neuroprotection by Minocycline Caused by Direct and Specific Scavenging of Peroxynitrite</dcterms:title>
    <dc:contributor>Drescher, Malte</dc:contributor>
    <dc:creator>Müller, Nathalie</dc:creator>
    <dcterms:abstract xml:lang="eng">Minocycline prevents oxidative protein modifications and damage in disease models associated with inflammatory glial activation and oxidative stress. Although the drug has been assumed to act by preventing the up-regulation of proinflammatory enzymes, we probed here its direct chemical interaction with reactive oxygen species. The antibiotic did not react with superoxide or •NO radicals, but peroxynitrite (PON) was scavenged in the range of ∼1 μm minocycline and below. The interaction of pharmacologically relevant minocycline concentrations with PON was corroborated in several assay systems and significantly exceeded the efficacy of other antibiotics. Minocycline was degraded during the reaction with PON, and the resultant products lacked antioxidant properties. The antioxidant activity of minocycline extended to cellular systems, because it prevented neuronal mitochondrial DNA damage and glutathione depletion. Maintenance of neuronal viability under PON stress was shown to be solely dependent on direct chemical scavenging by minocycline. We chose α-synuclein (ASYN), known from Parkinsonian pathology as a biologically relevant target in chemical and cellular nitration reactions. Submicromolar concentrations of minocycline prevented tyrosine nitration of ASYN by PON. Mass spectrometric analysis revealed that minocycline impeded nitrations more effectively than methionine oxidations and dimerizations of ASYN, which are secondary reactions under PON stress. Thus, PON scavenging at low concentrations is a novel feature of minocycline and may help to explain its pharmacological activity.</dcterms:abstract>
    <dc:contributor>Robotta, Marta</dc:contributor>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/13542/1/J.%20Biol.%20Chem.-2011-Schildknecht.pdf"/>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-02-29T23:25:05Z</dcterms:available>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/52"/>
    <dc:contributor>Leist, Marcel</dc:contributor>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/52"/>
    <dc:creator>Leist, Marcel</dc:creator>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-05-30T09:13:52Z</dc:date>
    <dc:rights>terms-of-use</dc:rights>
    <dcterms:bibliographicCitation>First publ. in: Journal of Biological Chemistry ; 286 (2011), 7. - S. 4991-5002</dcterms:bibliographicCitation>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/13542/1/J.%20Biol.%20Chem.-2011-Schildknecht.pdf"/>
    <dc:creator>Robotta, Marta</dc:creator>
    <dc:creator>Pape, Regina</dc:creator>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/13542"/>
    <dcterms:issued>2011-02-18</dcterms:issued>
    <dc:creator>Schildknecht, Stefan</dc:creator>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
  </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
Ja
Begutachtet
Diese Publikation teilen