Background
Sirtuin 1 (SIRT1) is an evolutionarily conserved NAD-dependent protein deacetylase that has been implicated in cell metabolism, differentiation, stress and DNA damage response, and the control of multidrug resistance in cancer. SIRT1 alters gene expression by deacetylating nuclear histones, NF-κB, p53, and FOXO transcription factors. CAY10602 was derived from high throughput screening for compounds that increase SIRT1-mediated deacetylation of a SIRT1-specific substrate. Functional assays show that CAY10602 dose-dependently suppresses the NF-κB-dependent induction of TNF-α by lipopolysaccharide in THP-1 cells, with approximately 75% inhibition achieved at 60 μM, without cytotoxicity. CAY10602 is at least 10 times more potent as a suppressor of TNF-α release than resveratrol. The effects of CAY10602 in other cellular processes remain to be determined.
Protocol
Cell experiment: | 3T3L1 mouse fibroblasts and THP-1 leukemia cells are used and cultured following the supplier’s recommendations.THP-1 cells are treated first with representative compounds (including CAY10602/compound 1) followed by addition of lipopolysaccharide(LPS). THP-1 cells are plated at a density of 1.2×106 cells/mL in 0.4 mL (0.5×106 cells/treatment) in 24-well culture plates. The cells are preincubated with representative test compounds (including CAY10602) at 2 concentrations (20 or 60 μM) for 1 h under general tissue culture conditions[1]. |
参考文献: [1]. Nayagam VM, et al. SIRT1 modulating compounds from high-throughput screening as anti-inflammatory and insulin-sensitizing agents. J Biomol Screen. 2006 Dec;11(8):959-67. |
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