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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/32404
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dc.contributor.authorPescador, Nuria-
dc.contributor.authorVillar, Diego-
dc.contributor.authorOrtiz-Barahona, Amaya-
dc.contributor.authorCuevas, Yolanda-
dc.contributor.authorGarcía-Bermejo, María Laura-
dc.contributor.authorLandázuri, Manuel O.-
dc.contributor.authorPeso, Luis del-
dc.date.accessioned2011-02-16T09:41:18Z-
dc.date.available2011-02-16T09:41:18Z-
dc.date.issued2010-03-12-
dc.identifier.citationPLoS ONE 5(3): e9644 (2010)es_ES
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10261/32404-
dc.descriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.-
dc.description.abstractWhen oxygen becomes limiting, cells reduce mitochondrial respiration and increase ATP production through anaerobic fermentation of glucose. The Hypoxia Inducible Factors (HIFs) play a key role in this metabolic shift by regulating the transcription of key enzymes of glucose metabolism. Here we show that oxygen regulates the expression of the muscle glycogen synthase (GYS1). Hypoxic GYS1 induction requires HIF activity and a Hypoxia Response Element within its promoter. GYS1 gene induction correlated with a significant increase in glycogen synthase activity and glycogen accumulation in cells exposed to hypoxia. Significantly, knockdown of either HIF1 alpha or GYS1 attenuated hypoxia-induced glycogen accumulation, while GYS1 overexpression was sufficient to mimic this effect. Altogether, these results indicate that GYS1 regulation by HIF plays a central role in the hypoxic accumulation of glycogen. Importantly, we found that hypoxia also upregulates the expression of UTP: glucose-1-phosphate urydylyltransferase (UGP2) and 1,4-alpha glucan branching enzyme (GBE1), two enzymes involved in the biosynthesis of glycogen. Therefore, hypoxia regulates almost all the enzymes involved in glycogen metabolism in a coordinated fashion, leading to its accumulation. Finally, we demonstrated that abrogation of glycogen synthesis, by knock-down of GYS1 expression, impairs hypoxic preconditioning, suggesting a physiological role for the glycogen accumulated during chronic hypoxia. In summary, our results uncover a novel effect of hypoxia on glucose metabolism, further supporting the central importance of metabolic reprogramming in the cellular adaptation to hypoxia.es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Sciencees_ES
dc.relation.isversionofPublisher's version-
dc.rightsopenAccesses_ES
dc.subjectProline hydroxylationes_ES
dc.subjectProlyl hydroxylationes_ES
dc.subjectMuscle cultureses_ES
dc.subjectHif-alphaes_ES
dc.titleHypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1es_ES
dc.typeartículoes_ES
dc.identifier.doi10.1371/journal.pone.0009644-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1371/journal.pone.0009644es_ES
dc.identifier.pmid20300197-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextopen-
item.openairetypeartículo-
item.fulltextWith Fulltext-
item.languageiso639-1en-
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