RGD Reference Report - Cardiac O-GlcNAc signaling is increased in hypertrophy and heart failure. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Cardiac O-GlcNAc signaling is increased in hypertrophy and heart failure.

Authors: Lunde, IG  Aronsen, JM  Kvaloy, H  Qvigstad, E  Sjaastad, I  Tonnessen, T  Christensen, G  Gronning-Wang, LM  Carlson, CR 
Citation: Lunde IG, etal., Physiol Genomics. 2012 Feb 1;44(2):162-72. doi: 10.1152/physiolgenomics.00016.2011. Epub 2011 Nov 29.
RGD ID: 9590202
Pubmed: PMID:22128088   (View Abstract at PubMed)
DOI: DOI:10.1152/physiolgenomics.00016.2011   (Journal Full-text)

Reversible protein O-GlcNAc modification has emerged as an essential intracellular signaling system in several tissues, including cardiovascular pathophysiology related to diabetes and acute ischemic stress. We tested the hypothesis that cardiac O-GlcNAc signaling is altered in chronic cardiac hypertrophy and failure of different etiologies. Global protein O-GlcNAcylation and the main enzymes regulating O-GlcNAc, O-GlcNAc transferase (OGT), O-GlcNAcase (OGA), and glutamine-fructose-6-phosphate amidotransferase (GFAT) were measured by immunoblot and/or real-time RT-PCR analyses of left ventricular tissue from aortic stenosis (AS) patients and rat models of hypertension, myocardial infarction (MI), and aortic banding (AB), with and without failure. We show here that global O-GlcNAcylation was increased by 65% in AS patients, by 47% in hypertensive rats, by 81 and 58% post-AB, and 37 and 60% post-MI in hypertrophic and failing hearts, respectively (P < 0.05). Noticeably, protein O-GlcNAcylation patterns varied in hypertrophic vs. failing hearts, and the most extensive O-GlcNAcylation was observed on proteins of 20-100 kDa in size. OGT, OGA, and GFAT2 protein and/or mRNA levels were increased by pressure overload, while neither was regulated by myocardial infarction. Pharmacological inhibition of OGA decreased cardiac contractility in post-MI failing hearts, demonstrating a possible role of O-GlcNAcylation in development of chronic cardiac dysfunction. Our data support the novel concept that O-GlcNAc signaling is altered in various etiologies of cardiac hypertrophy and failure, including human aortic stenosis. This not only provides an exciting basis for discovery of new mechanisms underlying pathological cardiac remodeling but also implies protein O-GlcNAcylation as a possible new therapeutic target in heart failure.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
OGTHumanaortic valve stenosis  IEP mRNA:increased expression:heart left ventricle (human)RGD 
OgtRataortic valve stenosis  ISOOGT (Homo sapiens)mRNA:increased expression:heart left ventricle (human)RGD 
OgtMouseaortic valve stenosis  ISOOGT (Homo sapiens)mRNA:increased expression:heart left ventricle (human)RGD 
OGTHumanCardiomegaly  ISOOgt (Rattus norvegicus)protein:increased expression:heart left ventricle (rat)RGD 
OgtRatCardiomegaly  IEP protein:increased expression:heart left ventricle (rat)RGD 
OgtMouseCardiomegaly  ISOOgt (Rattus norvegicus)protein:increased expression:heart left ventricle (rat)RGD 
OGTHumancongestive heart failure  ISOOgt (Rattus norvegicus)protein:increased expression:heart left ventricle (rat)RGD 
OgtRatcongestive heart failure  IEP protein:increased expression:heart left ventricle (rat)RGD 
OgtMousecongestive heart failure  ISOOgt (Rattus norvegicus)protein:increased expression:heart left ventricle (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ogt  (O-linked N-acetylglucosamine (GlcNAc) transferase)

Genes (Mus musculus)
Ogt  (O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase))

Genes (Homo sapiens)
OGT  (O-linked N-acetylglucosamine (GlcNAc) transferase)


Additional Information