Acute regulation of cardiac metabolism by the hexosamine biosynthesis pathway and protein O-GlcNAcylation

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dc.contributor.authorBeşikçi, Arzu Onay
dc.contributor.departmentDil ve Tarih-Coğrafya Fakültesitr_TR
dc.date.accessioned2020-02-17T18:53:37Z
dc.date.available2020-02-17T18:53:37Z
dc.date.issued2011
dc.description.abstractObjective: The hexosamine biosynthesis pathway (HBP) flux and protein O-linked N-acetyl-glucosamine (O-GlcNAc) levels have been implicated in mediating the adverse effects of diabetes in the cardiovascular system. Activation of these pathways with glucosamine has been shown to mimic some of the diabetes-induced functional and structural changes in the heart; however, the effect on cardiac metabolism is not known. Therefore, the primary goal of this study was to determine the effects of glucosamine on cardiac substrate utilization. Methods: Isolated rat hearts were perfused with glucosamine (0-10 mM) to increase HBP flux under normoxic conditions. Metabolic fluxes were determined by 13C-NMR isotopomer analysis; UDP-GlcNAc a precursor of O-GlcNAc synthesis was assessed by HPLC and immunoblot analysis was used to determine O-GlcNAc levels, phospho- and total levels of AMPK and ACC, and membrane levels of FAT/CD36. Results: Glucosamine caused a dose dependent increase in both UDP-GlcNAc and O-GlcNAc levels, which was associated with a significant increase in palmitate oxidation with a concomitant decrease in lactate and pyruvate oxidation. There was no effect of glucosamine on AMPK or ACC phosphorylation; however, membrane levels of the fatty acid transport protein FAT/CD36 were increased and preliminary studies suggest that FAT/CD36 is a potential target for O-GlcNAcylation. Conclusion/Interpretation: These data demonstrate that acute modulation of HBP and protein O-GlcNAcylation in the heart stimulates fatty acid oxidation, possibly by increasing plasma membrane levels of FAT/CD36, raising the intriguing possibility that the HBP and O-GlcNAc turnover represent a novel, glucose dependent mechanism for regulating cardiac metabolism. © 2011 Laczy et al.tr_TR
dc.description.indexScopus
dc.description.indexWos
dc.identifier.endpage9tr_TR
dc.identifier.issn/e-issn1932-6203
dc.identifier.issue4tr_TR
dc.identifier.othere18417tr_TR
dc.identifier.startpage1tr_TR
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0018417tr_TR
dc.identifier.urihttp://hdl.handle.net/20.500.12575/69670
dc.identifier.volume6tr_TR
dc.language.isoentr_TR
dc.relation.isversionof10.1371/journal.pone.0018417tr_TR
dc.relation.journalPLoS ONEtr_TR
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıtr_TR
dc.rightsCC0 1.0 Universal*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectacetyl coenzyme A carboxylasetr_TR
dc.subjectadenylate kinasetr_TR
dc.subjectadenylate kinasetr_TR
dc.titleAcute regulation of cardiac metabolism by the hexosamine biosynthesis pathway and protein O-GlcNAcylationtr_TR
dc.typeArticletr_TR

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