SIRT1 activation mediates heat-induced survival of UVB damaged Keratinocytes

BMC Dermatology

Research Article

Anthony David¹  Sandrine Kurdykowski¹  Pascal Descargues¹  Leslie Calapre²  Elin S. Gray²  Mel Ziman³ 

[1] GENOSKIN Centre Pierre Potier, Oncopole, Toulouse, France;School of Medical Science, Edith Cowan University, 270 Joondalup Drive, Joondalup, 6027, Perth, WA, Australia;School of Medical Science, Edith Cowan University, 270 Joondalup Drive, Joondalup, 6027, Perth, WA, Australia;School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, WA, Australia;

关键词: Heat stress;    UVB;    Keratinocytes;    Apoptosis;    p53;    SIRT1;    p53 deacetylation;   

DOI  :  10.1186/s12895-017-0060-y

 received in 2016-12-02, accepted in 2017-06-02,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundExposure to heat stress after UVB irradiation induces a reduction of apoptosis, resulting in survival of DNA damaged human keratinocytes. This heat-mediated evasion of apoptosis appears to be mediated by activation of SIRT1 and inactivation of p53 signalling. In this study, we assessed the role of SIRT1 in the inactivation of p53 signalling and impairment of DNA damage response in UVB plus heat exposed keratinocytes.ResultsActivation of SIRT1 after multiple UVB plus heat exposures resulted in increased p53 deacetylation at K382, which is known to affect its binding to specific target genes. Accordingly, we noted decreased apoptosis and down regulation of the p53 targeted pro-apoptotic gene BAX and the DNA repair genes ERCC1 and XPC after UVB plus heat treatments. In addition, UVB plus heat induced increased expression of the cell survival gene Survivin and the proliferation marker Ki67. Notably, keratinocytes exposed to UVB plus heat in the presence of the SIRT1 inhibitor, Ex-527, showed a similar phenotype to those exposed to UV alone; i.e. an increase in p53 acetylation, increased apoptosis and low levels of Survivin.ConclusionThis study demonstrate that heat-induced SIRT1 activation mediates survival of DNA damaged keratinocytes through deacetylation of p53 after exposure to UVB plus heat

【 授权许可】

CC BY   
© The Author(s). 2017