Publikationstyp: | Zeitschriftenartikel |
URI (zitierfähiger Link): | http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-111521 |
Autor/innen: | Fahrer, Jörg; Wagner, Silvia; Bürkle, Alexander; Königsrainer, Alfred |
Erscheinungsjahr: | 2009 |
Erschienen in: | Biochemical and Biophysical Research Communications ; 386 (2009), 1. - S. 232-236. - ISSN 0006-291X. - eISSN 1090-2104 |
Pubmed ID: | 19523443 |
DOI (zitierfähiger Link): | https://dx.doi.org/10.1016/j.bbrc.2009.06.022 |
Zusammenfassung: |
Rapamycin is an immunosuppressive drug, which inhibits the mammalian target of rapamycin (mTOR) kinase activity inducing changes in cell proliferation. Synthesis of poly(ADP-ribose) (PAR) is an immediate cellular response to genotoxic stress catalyzed mostly by poly(ADP-ribose) polymerase 1 (PARP-1), which is also controlled by signaling pathways. Therefore, we investigated whether rapamycin affects PAR production. Strikingly, rapamycin inhibited PAR synthesis in living fibroblasts in a dose-dependent manner as monitored by immunofluorescence. PARP-1 activity was then assayed in vitro, revealing that down-regulation of cellular PAR production by rapamycin was apparently not due to competitive PARP-1 inhibition. Further studies showed that rapamycin did not influence the cellular NAD pool and the activation of PARP-1 in extracts of pretreated fibroblasts. Collectively, our data suggest that inhibition of cellular PAR synthesis by rapamycin is mediated by formation of a detergent-sensitive complex in living cells, and that rapamycin may have a potential as therapeutic PARP inhibitor.
|
Fachgebiet (DDC): | 570 Biowissenschaften, Biologie |
Schlagwörter: | Rapamycin, mTOR, Poly(ADP-ribosyl)ation, PARP inhibitor, Fibroblasts |
Link zur Lizenz: | Nutzungsbedingungen |
Universitätsbibliographie: | Ja |
FAHRER, Jörg, Silvia WAGNER, Alexander BÜRKLE, Alfred KÖNIGSRAINER, 2009. Rapamycin inhibits poly(ADP-ribosyl)ation in intact cells. In: Biochemical and Biophysical Research Communications. 386(1), pp. 232-236. ISSN 0006-291X. eISSN 1090-2104. Available under: doi: 10.1016/j.bbrc.2009.06.022
@article{Fahrer2009Rapam-1115, title={Rapamycin inhibits poly(ADP-ribosyl)ation in intact cells}, year={2009}, doi={10.1016/j.bbrc.2009.06.022}, number={1}, volume={386}, issn={0006-291X}, journal={Biochemical and Biophysical Research Communications}, pages={232--236}, author={Fahrer, Jörg and Wagner, Silvia and Bürkle, Alexander and Königsrainer, Alfred} }
<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/123456789/1115"> <dc:language>eng</dc:language> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-23T09:06:14Z</dcterms:available> <dcterms:abstract xml:lang="eng">Rapamycin is an immunosuppressive drug, which inhibits the mammalian target of rapamycin (mTOR) kinase activity inducing changes in cell proliferation. Synthesis of poly(ADP-ribose) (PAR) is an immediate cellular response to genotoxic stress catalyzed mostly by poly(ADP-ribose) polymerase 1 (PARP-1), which is also controlled by signaling pathways. Therefore, we investigated whether rapamycin affects PAR production. Strikingly, rapamycin inhibited PAR synthesis in living fibroblasts in a dose-dependent manner as monitored by immunofluorescence. PARP-1 activity was then assayed in vitro, revealing that down-regulation of cellular PAR production by rapamycin was apparently not due to competitive PARP-1 inhibition. Further studies showed that rapamycin did not influence the cellular NAD pool and the activation of PARP-1 in extracts of pretreated fibroblasts. Collectively, our data suggest that inhibition of cellular PAR synthesis by rapamycin is mediated by formation of a detergent-sensitive complex in living cells, and that rapamycin may have a potential as therapeutic PARP inhibitor.</dcterms:abstract> <dcterms:issued>2009</dcterms:issued> <dc:contributor>Wagner, Silvia</dc:contributor> <dc:contributor>Königsrainer, Alfred</dc:contributor> <dc:creator>Bürkle, Alexander</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:contributor>Bürkle, Alexander</dc:contributor> <dc:creator>Wagner, Silvia</dc:creator> <dc:creator>Fahrer, Jörg</dc:creator> <dcterms:title>Rapamycin inhibits poly(ADP-ribosyl)ation in intact cells</dcterms:title> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/1115/1/Fahrer_opus-111521.pdf"/> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/1115/1/Fahrer_opus-111521.pdf"/> <dcterms:bibliographicCitation>Publ. in: Biochemical and Biophysical Research Communications 386 (2009), 1, pp. 232-236</dcterms:bibliographicCitation> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-23T09:06:14Z</dc:date> <dc:contributor>Fahrer, Jörg</dc:contributor> <dcterms:rights rdf:resource="https://kops.uni-konstanz.de/page/termsofuse"/> <dc:creator>Königsrainer, Alfred</dc:creator> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/1115"/> <dc:rights>terms-of-use</dc:rights> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> </rdf:Description> </rdf:RDF>
Fahrer_opus-111521.pdf | 6 |