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dc.contributor.authorCarrillo, Ana-
dc.contributor.authorMonreal, Yolanda-
dc.contributor.authorRamírez, Pablo-
dc.contributor.authorMarín, Luis-
dc.contributor.authorParrilla, Pascual-
dc.contributor.authorOliver, Francisco Javier-
dc.contributor.authorYélamos, José-
dc.date.accessioned2008-10-07T10:53:14Z-
dc.date.available2008-10-07T10:53:14Z-
dc.date.issued2004-02-03-
dc.identifier.citationNucleic Acids Research 32(3):757-766 (2004)en_US
dc.identifier.issn0305-1048-
dc.identifier.urihttp://hdl.handle.net/10261/7575-
dc.descriptionThe original publication is a available at www.oxfordjournals.org.-- 10 pp.en_US
dc.description.abstract[EN] Poly(ADP-ribose) polymerase-1 (PARP-1) has been involved in endothelial cell dysfunction associated with various pathophysiological conditions. The intrinsic mechanism of PARP-1-mediated endothelial cell dysfunction could be related to PARP-1 overactivation, NAD+ consumption and ATP depletion. An alternative way could involve transcription regulation. By using high-density microarrays, we examined early tumor necrosis factor α(TNF- α)- stimulated gene expression profiles in PARP-1+/+ and PARP-1-/- murine heart endothelial cells. TNF-α modulated a significant number of genes in both cell types. We have identified a set of genes whose expression in response to TNF-a is modulated by PARP-1, whereas the expression of others is PARP- 1-independent. Up-regulation of several genes involved in the inflammatory response is hampered in the absence of PARP-1. Moreover, NF-қB-dependent transcriptional activation is partially inhibited in PARP-1-/- compared to PARP-1+/+ cells. However, we found that PARP-1 might also silence transcription of several NF-қB target genes. Overall, our results show that PARP-1 is regulating the expression of genes by the endothelial cells both in a positive and a negative fashion, with the final effects depending on the gene. Individual studies of these genes are now necessary to clarify the intrinsic mechanism by which PARP-1 is controlling transcription and thereby finding out different therapeutic approaches involving PARP-1.en_US
dc.description.sponsorshipA.C. is a recipient of a fellowship from Fundación Séneca. J.Y. is an Investigator from the Ramón y Cajal Program (Spanish Ministerio de Ciencia y Tecnología). This work was supported by the Instituto de Salud Carlos III Grants PI021138 and C03/02.en_US
dc.format.extent317564 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.rightsopenAccessen_US
dc.titleTranscription regulation of TNF-α-early response genes by poly(ADP-ribose) polymerase-1 in murine heart endothelial cellsen_US
dc.typeartículoen_US
dc.identifier.doi10.1093/nar/gkh239-
dc.description.peerreviewedPeer revieweden_US
dc.relation.publisherversionhttp://dx.doi.org/10.1093/nar/gkh239en_US
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