RGD Reference Report - Sirtuin 6 protects cardiomyocytes from hypertrophy in vitro via inhibition of NF-kappaB-dependent transcriptional activity. - Rat Genome Database

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Sirtuin 6 protects cardiomyocytes from hypertrophy in vitro via inhibition of NF-kappaB-dependent transcriptional activity.

Authors: Yu, SS  Cai, Y  Ye, JT  Pi, RB  Chen, SR  Liu, PQ  Shen, XY  Ji, Y 
Citation: Yu SS, etal., Br J Pharmacol. 2013 Jan;168(1):117-28. doi: 10.1111/j.1476-5381.2012.01903.x.
RGD ID: 9586060
Pubmed: PMID:22335191   (View Abstract at PubMed)
PMCID: PMC3570008   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1476-5381.2012.01903.x   (Journal Full-text)

BACKGROUND AND PURPOSE: Sirtuin 6 (SIRT6) is involved in regulation of glucose and fat metabolism. However, its possible contribution to cardiac dysfunction remains to be determined. In the present study, the effect of SIRT6 on cardiac hypertrophy induced by angiotensin II (AngII) and the underlying molecular mechanisms were investigated. EXPERIMENTAL APPROACH: The expression and deacetylase activity of SIRT6 were measured in hypertrophic cardiomyocytes induced by AngII. After SIRT6 overexpression by transfection, or depletion by RNA interference in neonatal rat cardiomyocytes, cellular hypertrophy was monitored by measuring cell surface area and the mRNA levels of hypertrophic biomarkers. Further, the interaction between SIRT6 and the transcription factor NF-kappaB was investigated by co-immunoprecipitation, confocal immunofluorescence microscopy and luciferase reporter gene assay. The expression and deacetylase activity of SIRT6 were measured in vivo, using the abdominal aortic constriction (AAC) model of cardiac hypertrophy in rats. KEY RESULTS: In AngII-induced hypertrophic cardiomyocytes and also in AAC-induced hypertrophic hearts, the expression of SIRT6 protein was upregulated, while its deacetylase activity was decreased. Overexpression of wild-type SIRT6 but not its catalytically inactive mutant, attenuated AngII-induced cardiomyocyte hypertrophy. We further demonstrated a physical interaction between SIRT6 and NF-kappaB catalytic subunit p65, whose transcriptional activity could be repressed by SIRT6 overexpression. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that SIRT6 suppressed cardiomyocyte hypertrophy in vitro via inhibition of NF-kappaB-dependent transcriptional activity and that this effect was dependent on its deacetylase activity.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SIRT6HumanCardiomegaly  ISOSirt6 (Rattus norvegicus) RGD 
Sirt6RatCardiomegaly  IEP  RGD 
Sirt6MouseCardiomegaly  ISOSirt6 (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Sirt6Ratpost-embryonic cardiac muscle cell growth involved in heart morphogenesis  IMP  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RelaRatprotein binding  IPISirt6 (Rattus norvegicus) RGD 
Sirt6Ratprotein binding  IPIRela (Rattus norvegicus) RGD 
Sirt6Ratprotein lysine deacetylase activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rela  (RELA proto-oncogene, NF-kB subunit)
Sirt6  (sirtuin 6)

Genes (Mus musculus)
Sirt6  (sirtuin 6)

Genes (Homo sapiens)
SIRT6  (sirtuin 6)


Additional Information