SIRT1 activation mediates heat-induced survival of UVB damaged Keratinocytes
Identifieur interne : 000404 ( Main/Merge ); précédent : 000403; suivant : 000405SIRT1 activation mediates heat-induced survival of UVB damaged Keratinocytes
Auteurs : Leslie Calapre ; Elin S. Gray ; Sandrine Kurdykowski [France] ; Anthony David [France] ; Pascal Descargues [France] ; Mel ZimanSource :
- BMC Dermatology [ 1471-5945 ] ; 2017.
Abstract
Exposure 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
Activation of SIRT1 after multiple UVB
This study demonstrate that heat-induced SIRT1 activation mediates survival of DNA damaged keratinocytes through deacetylation of p53 after exposure to UVB
The online version of this article (doi:10.1186/s12895-017-0060-y) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12895-017-0060-y
PubMed: 28601088
PubMed Central: 5466784
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Exposure 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 <italic>plus</italic>
heat exposed keratinocytes.</p>
</sec>
<sec><title>Results</title>
<p>Activation of SIRT1 after multiple UVB <italic>plus</italic>
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 <italic>BAX</italic>
and the DNA repair genes <italic>ERCC1</italic>
and <italic>XPC</italic>
after UVB <italic>plus</italic>
heat treatments. In addition, UVB <italic>plus</italic>
heat induced increased expression of the cell survival gene <italic>Survivin</italic>
and the proliferation marker Ki67. Notably, keratinocytes exposed to UVB <italic>plus</italic>
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 <italic>Survivin</italic>
.</p>
</sec>
<sec><title>Conclusion</title>
<p>This study demonstrate that heat-induced SIRT1 activation mediates survival of DNA damaged keratinocytes through deacetylation of p53 after exposure to UVB <italic>plus</italic>
heat</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s12895-017-0060-y) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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<author><name sortKey="Gerstung, M" uniqKey="Gerstung M">M Gerstung</name>
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<author><name sortKey="Ellis, P" uniqKey="Ellis P">P Ellis</name>
</author>
<author><name sortKey="Van Loo, P" uniqKey="Van Loo P">P Van Loo</name>
</author>
<author><name sortKey="Mclaren, S" uniqKey="Mclaren S">S McLaren</name>
</author>
<author><name sortKey="Wedge, Dc" uniqKey="Wedge D">DC Wedge</name>
</author>
<author><name sortKey="Fullam, A" uniqKey="Fullam A">A Fullam</name>
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<author><name sortKey="Alexandrov, Lb" uniqKey="Alexandrov L">LB Alexandrov</name>
</author>
<author><name sortKey="Tubio, Jm" uniqKey="Tubio J">JM Tubio</name>
</author>
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