Journal
IMMUNE NETWORK
Volume 16, Issue 3, Pages 183-188Publisher
KOREA ASSOC IMMUNOLOGISTS
DOI: 10.4110/in.2016.16.3.183
Keywords
Sirtuin; Senescence; Tenovin-1; EX527
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Funding
- National Research Foundation (NRF) - Ministry of Science, ICT & Future Planning [2015R1C1A2A01053928]
- Gyeongsang National University
- National Research Foundation of Korea [2015R1C1A2A01053928] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Sirtuin family members with lysine deacetylase activity are known to play an important role in anti-aging and longevity. Cellular senescence is one of the hallmarks of aging, and downregulation of sirtuin is reported to induce premature senescence. In this study, we investigated the effects of small-molecule sirtuin inhibitors on cellular senescence. Various small molecules such as tenovin-1 and EX527 were employed for direct sirtuin activity inhibition. U251, SNB-75, and U87MG glioblastoma cells treated with sirtuin inhibitors exhibited phenotypes with nuclear enlargement. Furthermore, treatment of rat primary astrocytes with tenovin-1 also increased the size of the nucleus. The activity of senescence-associated beta-galactosidase, a marker of cellular senescence, was induced by tenovin-1 and EX527 treatment in U87MG glioblastoma cells. Consistent with the senescent phenotype, treatment with tenovin-1 increased p53 expression in U87MG cells. This study demonstrated the senescence-inducing effect of sirtuin inhibitors, which are potentially useful tools for senescence research.
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