RGD Reference Report - Augmented protein kinase C-alpha-induced myofilament protein phosphorylation contributes to myofilament dysfunction in experimental congestive 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

Augmented protein kinase C-alpha-induced myofilament protein phosphorylation contributes to myofilament dysfunction in experimental congestive heart failure.

Authors: Belin, RJ  Sumandea, MP  Allen, EJ  Schoenfelt, K  Wang, H  Solaro, RJ  De Tombe, PP 
Citation: Belin RJ, etal., Circ Res. 2007 Jul 20;101(2):195-204. Epub 2007 Jun 7.
RGD ID: 2292480
Pubmed: PMID:17556659   (View Abstract at PubMed)
DOI: DOI:10.1161/CIRCRESAHA.107.148288   (Journal Full-text)

It is becoming clear that upregulated protein kinase C (PKC) signaling plays a role in reduced ventricular myofilament contractility observed in congestive heart failure. However, data are scant regarding which PKC isozymes are involved. There is evidence that PKC-alpha may be of particular importance. Here, we examined PKC-alpha quantity, activity, and signaling to myofilaments in chronically remodeled myocytes obtained from rats in either early heart failure or end-stage congestive heart failure. Immunoblotting revealed that PKC-alpha expression and activation was unaltered in early heart failure but increased in end-stage congestive heart failure. Left ventricular myocytes were isolated by mechanical homogenization, Triton-skinned, and attached to micropipettes that projected from a force transducer and motor. Myofilament function was characterized by an active force-[Ca(2+)] relation to obtain Ca(2+)-saturated maximal force (F(max)) and myofilament Ca(2+) sensitivity (indexed by EC(50)) before and after incubation with PKC-alpha, protein phosphatase type 1 (PP1), or PP2a. PKC-alpha treatment induced a 30% decline in F(max) and 55% increase in the EC(50) in control cells but had no impact on myofilament function in failing cells. PP1-mediated dephosphorylation increased F(max) (15%) and decreased EC(50) ( approximately 20%) in failing myofilaments but had no effect in control cells. PP2a-dependent dephosphorylation had no effect on myofilament function in either group. Lastly, PP1 dephosphorylation restored myofilament function in control cells hyperphosphorylated with PKC-alpha. Collectively, our results suggest that in end-stage congestive heart failure, the myofilament proteins exist in a hyperphosphorylated state attributable, in part, to increased activity and signaling of PKC-alpha.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
congestive heart failure  ISOPrkca (Rattus norvegicus)2292480; 2292480protein:increased expression and increased phosphorylation:heart left ventricleRGD 
congestive heart failure  IEP 2292480protein:increased expression and increased phosphorylation:heart left ventricleRGD 

Objects Annotated

Genes (Rattus norvegicus)
Prkca  (protein kinase C, alpha)

Genes (Mus musculus)
Prkca  (protein kinase C, alpha)

Genes (Homo sapiens)
PRKCA  (protein kinase C alpha)


Additional Information