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l-Selegiline Potentiates the Cellular Poly(ADP-Ribosyl)ationResponse to Ionizing Radiation

l-Selegiline Potentiates the Cellular Poly(ADP-Ribosyl)ationResponse to Ionizing Radiation

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BRABECK, Christine, Ragen PFEIFFER, Alan LEAKE, Sascha BENEKE, Ralph MEYER, Alexander BÜRKLE, 2003. l-Selegiline Potentiates the Cellular Poly(ADP-Ribosyl)ationResponse to Ionizing Radiation. In: Journal of Pharmacology and Experimental Therapeutics. American Society for Pharmacology and Experimental Therapeutics. 306(3), pp. 973-979. ISSN 0022-3565. eISSN 1521-0103. Available under: doi: 10.1124/jpet.103.051342

@article{Brabeck2003-09lSele-52313, title={l-Selegiline Potentiates the Cellular Poly(ADP-Ribosyl)ationResponse to Ionizing Radiation}, year={2003}, doi={10.1124/jpet.103.051342}, number={3}, volume={306}, issn={0022-3565}, journal={Journal of Pharmacology and Experimental Therapeutics}, pages={973--979}, author={Brabeck, Christine and Pfeiffer, Ragen and Leake, Alan and Beneke, Sascha and Meyer, Ralph and Bürkle, Alexander} }

<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/rdf/resource/123456789/52313"> <dc:contributor>Bürkle, Alexander</dc:contributor> <dc:creator>Leake, Alan</dc:creator> <dc:contributor>Leake, Alan</dc:contributor> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/52313"/> <dc:creator>Pfeiffer, Ragen</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Meyer, Ralph</dc:contributor> <dcterms:title>l-Selegiline Potentiates the Cellular Poly(ADP-Ribosyl)ationResponse to Ionizing Radiation</dcterms:title> <dc:creator>Brabeck, Christine</dc:creator> <dc:creator>Beneke, Sascha</dc:creator> <dc:creator>Meyer, Ralph</dc:creator> <dc:rights>terms-of-use</dc:rights> <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/> <dc:language>eng</dc:language> <dc:creator>Bürkle, Alexander</dc:creator> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-01-08T09:28:57Z</dc:date> <dc:contributor>Pfeiffer, Ragen</dc:contributor> <dc:contributor>Brabeck, Christine</dc:contributor> <dcterms:issued>2003-09</dcterms:issued> <dc:contributor>Beneke, Sascha</dc:contributor> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-01-08T09:28:57Z</dcterms:available> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:abstract xml:lang="eng">DNA strand breaks induced by alkylating agents, oxidants, or ionizingradiation trigger the covalent modification of nuclear proteins withpoly(ADP-ribose), which is catalyzed for the most part by poly(ADP-ribose)polymerase-1 and plays a role in DNA base-excision repair.Poly(ADP-ribosyl)ation capacity of mononuclear blood cells correlatespositively with life span of mammalian species. Here, we show that l-selegiline, an anti-Parkinson drug with neuroprotective activityand life span-extending effect in laboratory animals, can potentiate γ-radiation-induced poly(ADP-ribose) formation in intact cells. COR4hamster cells were incubated with l-selegiline (50 nM) for varioustime periods, followed by γ-irradiation (45 Gy). Quantification ofcellular poly(ADP-ribose) levels at 10 min after starting the irradiationrevealed significant increases (up to 1.8-fold) in cells preincubated with thedrug for 8 h to 7 days compared with drug-free irradiated controls. There wasno selegiline-induced change in poly(ADP-ribose) levels of unirradiated cellsnor in basal or radiation-induced DNA strand breaks, respectively.Surprisingly, poly(ADP-ribose) polymerase-1 protein was down-regulated by l-selegiline treatment. Addition of l-selegiline topurified poly(ADP-ribose) polymerase-1 did not alter enzymatic activity. Inconclusion, the results of the present study identify a novel intervention topotentiate the cellular poly(ADP-ribosyl)ation response. We hypothesize thatthe effect of l-selegiline is due to modulation of accessoryproteins regulating poly(ADP-ribose) polymerase-1 activity and that increasedcellular poly- (ADP-ribosyl)ation capacity may contribute to theneuroprotective potential and/or life span extension afforded by l-selegiline.</dcterms:abstract> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> </rdf:Description> </rdf:RDF>

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