Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

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.
Pubmed: (View Article at PubMed) PMID:22335191
DOI: Full-text: DOI:10.1111/j.1476-5381.2012.01903.x

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.


Disease Annotations
Gene Ontology Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 9586060
Created: 2014-09-26
Species: All species
Last Modified: 2014-09-26
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.