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Transcription regulation of TNF-α-early response genes by poly(ADP-ribose) polymerase-1 in murine heart endothelial cells

AuthorsCarrillo, Ana; Monreal, Yolanda; Ramírez, Pablo; Marín, Luis; Parrilla, Pascual; Oliver, Francisco Javier; Yélamos, José
Issue Date3-Feb-2004
PublisherOxford University Press
CitationNucleic Acids Research 32(3):757-766 (2004)
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.
DescriptionThe original publication is a available at www.oxfordjournals.org.-- 10 pp.
Publisher version (URL)http://dx.doi.org/10.1093/nar/gkh239
Appears in Collections:(IPBLN) Artículos
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