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http://purl.uniprot.org/citations/18285568http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18285568http://www.w3.org/2000/01/rdf-schema#comment"

Background

The modification of proteins with O-linked beta-N-acetylglucosamine (O-GlcNAc) represents a key posttranslational modification that modulates cellular function. Previous data suggest that O-GlcNAc may act as an intracellular metabolic or stress sensor, linking glucose metabolism to cellular function. Considering this, we hypothesized that augmentation of O-GlcNAc levels represents an endogenously recruitable mechanism of cardioprotection.

Methods and results

In mouse hearts subjected to in vivo ischemic preconditioning, O-GlcNAc levels were significantly elevated. Pharmacological augmentation of O-GlcNAc levels in vivo was sufficient to reduce myocardial infarct size. We investigated the influence of O-GlcNAc levels on cardiac injury at the cellular level. Lethal oxidant stress of cardiac myocytes produced a time-dependent loss of cellular O-GlcNAc levels. This pathological response was largely reversible by pharmacological augmentation of O-GlcNAc levels and was associated with improved cardiac myocyte survival. The diminution of O-GlcNAc levels occurred synchronously with the loss of mitochondrial membrane potential in isolated cardiac myocytes. Pharmacological enhancement of O-GlcNAc levels attenuated the loss of mitochondrial membrane potential. Proteomic analysis identified voltage-dependent anion channel as a potential target of O-GlcNAc modification. Mitochondria isolated from adult mouse hearts with elevated O-GlcNAc levels had more O-GlcNAc-modified voltage-dependent anion channel and were more resistant to calcium-induced swelling than cardiac mitochondria from vehicle mice.

Conclusions

O-GlcNAc signaling represents a unique endogenously recruitable mechanism of cardioprotection that may involve direct modification of mitochondrial proteins critical for survival such as voltage-dependent anion channel."xsd:string
http://purl.uniprot.org/citations/18285568http://purl.org/dc/terms/identifier"doi:10.1161/circulationaha.107.730515"xsd:string
http://purl.uniprot.org/citations/18285568http://purl.uniprot.org/core/author"Hart G.W."xsd:string
http://purl.uniprot.org/citations/18285568http://purl.uniprot.org/core/author"Zachara N.E."xsd:string
http://purl.uniprot.org/citations/18285568http://purl.uniprot.org/core/author"Bhatnagar A."xsd:string
http://purl.uniprot.org/citations/18285568http://purl.uniprot.org/core/author"Jones S.P."xsd:string
http://purl.uniprot.org/citations/18285568http://purl.uniprot.org/core/author"Marban E."xsd:string
http://purl.uniprot.org/citations/18285568http://purl.uniprot.org/core/author"Teshima Y."xsd:string
http://purl.uniprot.org/citations/18285568http://purl.uniprot.org/core/author"Hill B.G."xsd:string
http://purl.uniprot.org/citations/18285568http://purl.uniprot.org/core/author"Ngoh G.A."xsd:string
http://purl.uniprot.org/citations/18285568http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18285568http://purl.uniprot.org/core/name"Circulation"xsd:string
http://purl.uniprot.org/citations/18285568http://purl.uniprot.org/core/pages"1172-1182"xsd:string
http://purl.uniprot.org/citations/18285568http://purl.uniprot.org/core/title"Cardioprotection by N-acetylglucosamine linkage to cellular proteins."xsd:string
http://purl.uniprot.org/citations/18285568http://purl.uniprot.org/core/volume"117"xsd:string
http://purl.uniprot.org/citations/18285568http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18285568
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