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Mechanism of succinate efflux upon reperfusion of the ischaemic heart

dc.contributor.authorPRAG, Hiran
dc.contributor.authorGRUSZCZYK, Anja
dc.contributor.authorHUANG, Margaret
dc.contributor.authorBEACH, Timothy
dc.contributor.authorYOUNG, Timothy
dc.contributor.authorTRONCI, Laura
dc.contributor.authorNIKITOPOULOU, Efterpi
dc.contributor.authorMULVEY, John
dc.contributor.authorASCIONE, Raimondo
dc.contributor.authorHADJIHAMBI, Anna
dc.contributor.authorSHATTOCK, Michael
dc.contributor.authorPELLERIN, Luc
dc.contributor.authorSAEB-PARSY, Kourosh
dc.contributor.authorFREZZA, Christian
dc.contributor.authorJAMES, Andrew
dc.contributor.authorKRIEG, Thomas
dc.contributor.authorMURPHY, Michael
dc.contributor.authorAKSENTIJEVIĆ, Dunja
dc.date.accessioned2021-10-07T16:27:32Z
dc.date.available2021-10-07T16:27:32Z
dc.date.issued2021-04-01
dc.identifier.issn0008-6363
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112564
dc.description.abstractEnAbstract Aims Succinate accumulates several-fold in the ischaemic heart and is then rapidly oxidized upon reperfusion, contributing to reactive oxygen species production by mitochondria. In addition, a significant amount of the accumulated succinate is released from the heart into the circulation at reperfusion, potentially activating the G-protein-coupled succinate receptor (SUCNR1). However, the factors that determine the proportion of succinate oxidation or release, and the mechanism of this release, are not known. Methods and results To address these questions, we assessed the fate of accumulated succinate upon reperfusion of anoxic cardiomyocytes, and of the ischaemic heart both ex vivo and in vivo. The release of accumulated succinate was selective and was enhanced by acidification of the intracellular milieu. Furthermore, pharmacological inhibition, or haploinsufficiency of the monocarboxylate transporter 1 (MCT1) significantly decreased succinate efflux from the reperfused heart. Conclusion Succinate release upon reperfusion of the ischaemic heart is mediated by MCT1 and is facilitated by the acidification of the myocardium during ischaemia. These findings will allow the signalling interaction between succinate released from reperfused ischaemic myocardium and SUCNR1 to be explored.
dc.language.isoen
dc.publisherOxford University Press (OUP)
dc.rights.urihttp://creativecommons.org/licenses/by/
dc.title.enMechanism of succinate efflux upon reperfusion of the ischaemic heart
dc.typeArticle de revue
dc.identifier.doi10.1093/cvr/cvaa148
dc.subject.halSciences du Vivant [q-bio]
bordeaux.journalCardiovascular Research
bordeaux.page1188-1201
bordeaux.volume117
bordeaux.hal.laboratoriesCentre de Résonance Magnétique des Systèmes Biologiques (CRMSB) - UMR 5536*
bordeaux.issue4
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierhal-03366637
hal.version1
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-03366637v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Cardiovascular%20Research&rft.date=2021-04-01&rft.volume=117&rft.issue=4&rft.spage=1188-1201&rft.epage=1188-1201&rft.eissn=0008-6363&rft.issn=0008-6363&rft.au=PRAG,%20Hiran&GRUSZCZYK,%20Anja&HUANG,%20Margaret&BEACH,%20Timothy&YOUNG,%20Timothy&rft.genre=article


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