PMID: 29465379Feb 22, 2018Paper

Effect of SIRT6 knockdown on NF-κB induction and on residual DNA damage in cultured human skin fibroblasts

Journal of Cosmetic Science
E C GoyartsN Pernodet

Abstract

SIRT6 is a member of the sirtuin family, which is involved in multiple cellular pathways related to aging, inflammation, epigenetics, and a variety of other cellular functions, including DNA repair (1). Multiple pathways involving different cellular functions are impacted by the deacetylase activity of SIRT6. Genomic integrity is maintained by the capacity of SIRT6 to modulate the accessibility of DNA repair proteins. Glucose metabolism is suppressed by SIRT6 via the deacetylation of histones located at the promoter regions of multiple glycolytic genes and the corepression of hypoxia-inducible factor-1α. SIRT6 is also a corepressor of nuclear factor (NF)-κB, silencing NF-κB target genes through the deacetylation of histones at their promoters’ regions. We used SIRT6 small-interfering RNA as a tool to modulate residual DNA damage and NF-κB expression in human dermal fibroblasts. We measured NF-κB levels in the presence or the absence of ultraviolet B (UVB). The impact of SIRT6 knockdown as shown by a decrease in SIRT6 messenger RNA levels resulted in residual DNA damage as evaluated by the comet assay. Our results show that NF-κB was increased significantly (up to 400%) due to SIRT6 silencing in the absence of UVB, illustrating ...Continue Reading

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