Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/34533
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Palomer Tarridas, Francesc Xavier | - |
dc.contributor.author | Álvarez Guardia, David | - |
dc.contributor.author | Davidson, Mercy M. | - |
dc.contributor.author | Chan, Tung O. | - |
dc.contributor.author | Feldman, Arthur M. | - |
dc.contributor.author | Vázquez Carrera, Manuel | - |
dc.date.accessioned | 2013-04-11T15:55:47Z | - |
dc.date.available | 2013-04-11T15:55:47Z | - |
dc.date.issued | 2011-05-23 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/2445/34533 | - |
dc.description.abstract | Pyruvate dehydrogenase kinase 4 (PDK4) inhibition by nuclear factor-κB (NF-κB) is related to a shift towards increased glycolysis during cardiac pathological processes such as cardiac hypertrophy and heart failure. The transcription factors estrogen-related receptor-α (ERRα) and peroxisome proliferator-activated receptor (PPAR) regulate PDK4 expression through the potent transcriptional coactivator PPARγ coactivator-1α (PGC-1α). NF-κB activation in AC16 cardiac cells inhibit ERRα and PPARβ/δ transcriptional activity, resulting in reduced PGC-1α and PDK4 expression, and an enhanced glucose oxidation rate. However, addition of the NF-κB inhibitor parthenolide to these cells prevents the downregulation of PDK4 expression but not ERRα and PPARβ/δ DNA binding activity, thus suggesting that additional transcription factors are regulating PDK4. Interestingly, a recent study has demonstrated that the transcription factor E2F1, which is crucial for cell cycle control, may regulate PDK4 expression. Given that NF-κB may antagonize the transcriptional activity of E2F1 in cardiac myocytes, we sought to study whether inflammatory processes driven by NF-κB can downregulate PDK4 expression in human cardiac AC16 cells through E2F1 inhibition. Protein coimmunoprecipitation indicated that PDK4 downregulation entailed enhanced physical interaction between the p65 subunit of NF-κB and E2F1. Chromatin immunoprecipitation analyses demonstrated that p65 translocation into the nucleus prevented the recruitment of E2F1 to the PDK4 promoter and its subsequent E2F1-dependent gene transcription. Interestingly, the NF-κB inhibitor parthenolide prevented the inhibition of E2F1, while E2F1 overexpression reduced interleukin expression in stimulated cardiac cells. Based on these findings, we propose that NF-κB acts as a molecular switch that regulates E2F1-dependent PDK4 gene transcription. | - |
dc.format.extent | 12 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Public Library of Science (PLoS) | - |
dc.relation.isformatof | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0019724 | - |
dc.relation.ispartof | PLoS One, 2011, vol. 6, num. 5, p. e19724 | - |
dc.relation.uri | http://dx.doi.org/10.1371/journal.pone.0019724 | - |
dc.rights | cc-by (c) Palomer Tarridas, Francesc Xavier et al., 2011 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) | - |
dc.subject.classification | Cor | - |
dc.subject.classification | Miocardi | - |
dc.subject.classification | Fisiologia cel·lular | - |
dc.subject.classification | Proteïnes | - |
dc.subject.classification | Transcripció genètica | - |
dc.subject.classification | Cèl·lules musculars | - |
dc.subject.other | Heart | - |
dc.subject.other | Myocardium | - |
dc.subject.other | Cell physiology | - |
dc.subject.other | Proteins | - |
dc.subject.other | Genetic transcription | - |
dc.subject.other | Muscle cells | - |
dc.title | The Interplay between NF-kappaB and E2F1 Coordinately Regulates Inflammation and Metabolism in Human Cardiac Cells | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 595696 | - |
dc.date.updated | 2013-04-11T15:55:47Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 21625432 | - |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
595696.pdf | 685.79 kB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License