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http://hdl.handle.net/2445/60799
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DC Field | Value | Language |
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dc.contributor.author | Soriano Zaragoza, Francesc X. (Francesc Xavier) | - |
dc.contributor.author | Léveillé, Frédéric | - |
dc.contributor.author | Papadia, Sofia | - |
dc.contributor.author | Bell, Karen F. S. | - |
dc.contributor.author | Puddifoot, Clare | - |
dc.contributor.author | Hardingham, Giles E. | - |
dc.date.accessioned | 2014-12-16T13:50:33Z | - |
dc.date.available | 2014-12-16T13:50:33Z | - |
dc.date.issued | 2010-03-20 | - |
dc.identifier.issn | 1523-0864 | - |
dc.identifier.uri | http://hdl.handle.net/2445/60799 | - |
dc.description.abstract | Transcriptional coactivators and corepressors often have multiple targets and can have opposing actions on transcription and downstream physiological events. The coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is under-expressed in Huntington's disease and is a regulator of antioxidant defenses and mitochondrial biogenesis. We show that in primary cortical neurons, expression of PGC-1α strongly promotes resistance to excitotoxic and oxidative stress in a cell autonomous manner, whereas knockdown increases sensitivity. In contrast, the transcriptional corepressor silencing mediator of retinoic acid and thyroid hormone receptors (SMRT) specifically antagonizes PGC-1α-mediated antioxidant effects. The antagonistic balance between PGC-1α and SMRT is upset in favor of PGC-1α by synaptic activity. Synaptic activity triggers nuclear export of SMRT reliant on multiple regions of the protein. Concommitantly, synaptic activity post-translationally enhances the transactivating potential of PGC-1α in a p38-dependent manner, as well as upregulating cyclic-AMP response element binding protein-dependent PGC-1α transcription. Activity-dependent targeting of PGC-1α results in enhanced gene expression mediated by the thyroid hormone receptor, a prototypical transcription factor coactivated by PGC-1α and repressed by SMRT. As a consequence of these events, SMRT is unable to antagonize PGC-1α-mediated resistance to oxidative stress in synaptically active neurons. Thus, PGC-1α and SMRT are antagonistic regulators of neuronal vulnerability to oxidative stress. Further, this coactivator<br>corepressor antagonism is regulated by the activity status of the cell, with implications for neuronal viability. | - |
dc.format.extent | 12 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Mary Ann Liebert, Inc. | - |
dc.relation.isformatof | Reproducció del document publicat a: http://dx.doi.org/10.1089/ars.2010.3568 | - |
dc.relation.ispartof | Antioxidants & Redox Signaling, 2010, vol. 14, num. 8, p. 1425-1436 | - |
dc.relation.uri | http://dx.doi.org/10.1089/ars.2010.3568 | - |
dc.rights | (c) Mary Ann Liebert, Inc., 2010 | - |
dc.source | Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia) | - |
dc.subject.classification | Neurones | - |
dc.subject.classification | Malalties neurodegeneratives | - |
dc.subject.classification | Regulació genètica | - |
dc.subject.classification | Corea de Huntington | - |
dc.subject.other | Neurons | - |
dc.subject.other | Neurodegenerative Diseases | - |
dc.subject.other | Genetic regulation | - |
dc.subject.other | Huntington's chorea | - |
dc.title | Neuronal activity controls the antagonistic between PGC-1α and SMRT in regulating antioxidant defences | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 604428 | - |
dc.date.updated | 2014-12-16T13:50:34Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia) |
Files in This Item:
File | Description | Size | Format | |
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604428.pdf | 506.62 kB | Adobe PDF | View/Open |
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