Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.

Detalles Bibliográficos
Autores: Pescador, Nuria, Villar, Diego, Ortiz-Barahona, Amaya, Cuevas, Yolanda, García-Bermejo, María Laura, Landázuri, Manuel O., Peso, Luis del
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/32404
Acceso en línea:http://hdl.handle.net/10261/32404
Access Level:acceso abierto
Palabra clave:Proline hydroxylation
Prolyl hydroxylation
Muscle cultures
Hif-alpha
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spelling Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1Pescador, NuriaVillar, DiegoOrtiz-Barahona, AmayaCuevas, YolandaGarcía-Bermejo, María LauraLandázuri, Manuel O.Peso, Luis delProline hydroxylationProlyl hydroxylationMuscle culturesHif-alphaThis is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.When 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.Peer reviewedPublic Library of Science201120112010info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/32404reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1371/journal.pone.0009644info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/324042026-05-22T06:33:51Z
dc.title.none.fl_str_mv Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1
title Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1
spellingShingle Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1
Pescador, Nuria
Proline hydroxylation
Prolyl hydroxylation
Muscle cultures
Hif-alpha
title_short Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1
title_full Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1
title_fullStr Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1
title_full_unstemmed Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1
title_sort Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1
dc.creator.none.fl_str_mv Pescador, Nuria
Villar, Diego
Ortiz-Barahona, Amaya
Cuevas, Yolanda
García-Bermejo, María Laura
Landázuri, Manuel O.
Peso, Luis del
author Pescador, Nuria
author_facet Pescador, Nuria
Villar, Diego
Ortiz-Barahona, Amaya
Cuevas, Yolanda
García-Bermejo, María Laura
Landázuri, Manuel O.
Peso, Luis del
author_role author
author2 Villar, Diego
Ortiz-Barahona, Amaya
Cuevas, Yolanda
García-Bermejo, María Laura
Landázuri, Manuel O.
Peso, Luis del
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Proline hydroxylation
Prolyl hydroxylation
Muscle cultures
Hif-alpha
topic Proline hydroxylation
Prolyl hydroxylation
Muscle cultures
Hif-alpha
description This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.
publishDate 2010
dc.date.none.fl_str_mv 2010
2011
2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/32404
url http://hdl.handle.net/10261/32404
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1371/journal.pone.0009644
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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