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dc.contributor.authorPardo, Beatriz-
dc.contributor.authorRodrigues, Tiago B.-
dc.contributor.authorContreras, Laura-
dc.contributor.authorLlorente-Folch, Irene-
dc.contributor.authorCerdán, Sebastián-
dc.contributor.authorSatrústegui, Jorgina-
dc.date.accessioned2013-05-22T09:14:46Z-
dc.date.available2013-05-22T09:14:46Z-
dc.date.issued2011-
dc.identifierdoi: 10.1038/jcbfm.2010.146-
dc.identifierissn: 0271-678X-
dc.identifiere-issn: 1559-7016-
dc.identifier.citationJournal of Cerebral Blood Flow and Metabolism 31: 90-101 (2011)-
dc.identifier.urihttp://hdl.handle.net/10261/76492-
dc.description.abstractThe glutamate-glutamine cycle faces a drain of glutamate by oxidation, which is balanced by the anaplerotic synthesis of glutamate and glutamine in astrocytes. De novo synthesis of glutamate by astrocytes requires an amino group whose origin is unknown. The deficiency in Aralar/AGC1, the main mitochondrial carrier for aspartate-glutamate expressed in brain, results in a drastic fall in brain glutamine production but a modest decrease in brain glutamate levels, which is not due to decreases in neuronal or synaptosomal glutamate content. In vivo 13C nuclear magnetic resonance labeling with 13C 2 acetate or (1- 13C) glucose showed that the drop in brain glutamine is due to a failure in glial glutamate synthesis. Aralar deficiency induces a decrease in aspartate content, an increase in lactate production, and lactate-to-pyruvate ratio in cultured neurons but not in cultured astrocytes, indicating that Aralar is only functional in neurons. We find that aspartate, but not other amino acids, increases glutamate synthesis in both control and aralar-deficient astrocytes, mainly by serving as amino donor. These findings suggest the existence of a neuron-to-astrocyte aspartate transcellular pathway required for astrocyte glutamate synthesis and subsequent glutamine formation. This pathway may provide a mechanism to transfer neuronal-born redox equivalents to mitochondria in astrocytes. © 2011 ISCBFM All rights reserved.-
dc.description.sponsorshipThis work was supported in part by Ministerio de Educación y Ciencia Grants BFU2008-04084/BMC (to JS) and SAF2008-01327 (to SC), Comunidad de Madrid Grants S-GEN-0269-2006 MITOLAB-CM (to JS) and S-BIO-2006-0170 MULTIMAG (to SC), European Union Grant LSHM-CT-2006-518153 (to JS), and Fundación Médica Mutua Madrileña (to BP).-
dc.language.isoeng-
dc.publisherNature Publishing Group-
dc.relationS2006/GEN-0269/MITOLAB-
dc.relationS2006/BIO-0170/MULTIMAG-
dc.rightsclosedAccess-
dc.titleBrain glutamine synthesis requires neuronal-born aspartate as amino donor for glial glutamate formation-
dc.typeartículo-
dc.identifier.doi10.1038/jcbfm.2010.146-
dc.date.updated2013-05-22T09:14:46Z-
dc.description.versionPeer Reviewed-
dc.contributor.funderMinisterio de Educación y Ciencia (España)-
dc.contributor.funderComunidad de Madrid-
dc.contributor.funderEuropean Commission-
dc.contributor.funderFundación Mutua Madrileña-
dc.relation.csic-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100008061es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100012818es_ES
dc.identifier.pmid20736955-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.cerifentitytypePublications-
item.languageiso639-1en-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextNo Fulltext-
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