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http://purl.uniprot.org/citations/22335191http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22335191http://www.w3.org/2000/01/rdf-schema#comment"

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-κB 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-κB 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-κB-dependent transcriptional activity and that this effect was dependent on its deacetylase activity."xsd:string
http://purl.uniprot.org/citations/22335191http://purl.org/dc/terms/identifier"doi:10.1111/j.1476-5381.2012.01903.x"xsd:string
http://purl.uniprot.org/citations/22335191http://purl.uniprot.org/core/author"Ji Y."xsd:string
http://purl.uniprot.org/citations/22335191http://purl.uniprot.org/core/author"Cai Y."xsd:string
http://purl.uniprot.org/citations/22335191http://purl.uniprot.org/core/author"Yu S.S."xsd:string
http://purl.uniprot.org/citations/22335191http://purl.uniprot.org/core/author"Chen S.R."xsd:string
http://purl.uniprot.org/citations/22335191http://purl.uniprot.org/core/author"Liu P.Q."xsd:string
http://purl.uniprot.org/citations/22335191http://purl.uniprot.org/core/author"Shen X.Y."xsd:string
http://purl.uniprot.org/citations/22335191http://purl.uniprot.org/core/author"Ye J.T."xsd:string
http://purl.uniprot.org/citations/22335191http://purl.uniprot.org/core/author"Pi R.B."xsd:string
http://purl.uniprot.org/citations/22335191http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/22335191http://purl.uniprot.org/core/name"Br J Pharmacol"xsd:string
http://purl.uniprot.org/citations/22335191http://purl.uniprot.org/core/pages"117-128"xsd:string
http://purl.uniprot.org/citations/22335191http://purl.uniprot.org/core/title"Sirtuin 6 protects cardiomyocytes from hypertrophy in vitro via inhibition of NF-kappaB-dependent transcriptional activity."xsd:string
http://purl.uniprot.org/citations/22335191http://purl.uniprot.org/core/volume"168"xsd:string
http://purl.uniprot.org/citations/22335191http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22335191
http://purl.uniprot.org/citations/22335191http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22335191
http://purl.uniprot.org/uniprot/A0A8I6APP5#attribution-23DC002C882486BC5E2D19C35909C291http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/22335191
http://purl.uniprot.org/uniprot/A0A8I6APP5#attribution-A9634049727CF8D1E464085B87CDF04Bhttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/22335191
http://purl.uniprot.org/uniprot/A6K863#attribution-23DC002C882486BC5E2D19C35909C291http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/22335191
http://purl.uniprot.org/uniprot/A6K863#attribution-A9634049727CF8D1E464085B87CDF04Bhttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/22335191
http://purl.uniprot.org/uniprot/#_A0A8I6APP5-mappedCitation-22335191http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22335191
http://purl.uniprot.org/uniprot/#_A0A8I6ATQ5-mappedCitation-22335191http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22335191
http://purl.uniprot.org/uniprot/#_A0A8I5ZMV7-mappedCitation-22335191http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22335191
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