合成白藜芦醇脂肪酸抑制Toll样受体2介导的细胞凋亡及Akt/糖原合成酶激酶3β信号通路的参与
Synthetic resveratrol aliphatic acid inhibits TLR2-mediated apoptosis and an involvement of Akt/GSK3beta pathway.
作者信息
Chen Lin, Zhang Yi, Sun Xiuli, Li Hui, LeSage Gene, Javer Avani, Zhang Xiumei, Wei Xinbing, Jiang Yulin, Yin Deling
机构信息
Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
出版信息
Bioorg Med Chem. 2009 Jul 1;17(13):4378-82. doi: 10.1016/j.bmc.2009.05.029. Epub 2009 May 18.
As resveratrol derivatives, resveratrol aliphatic acids were synthesized in our laboratory. Previously, we reported the improved pharmaceutical properties of the compounds compared to resveratrol, including better solubility in water and much tighter binding with human serum albumin. Here, we investigate the role of resveratrol aliphatic acids in Toll-like receptor 2 (TLR2)-mediated apoptosis. We showed that resveratrol aliphatic acid (R6A) significantly inhibits the expression of TLR2. In addition, overexpression of TLR2 in HEK293 cells caused a significant decrease in apoptosis after R6A treatment. Moreover, inhibition of TLR2 by R6A decreases serum deprivation-reduced the levels of phosphorylated Akt and phosphorylated glycogen synthase kinase 3beta (GSK3beta). Our study thus demonstrates that the resveratrol aliphatic acid inhibits cell apoptosis through TLR2 by the involvement of Akt/GSK3beta pathway.
作为白藜芦醇衍生物，白藜芦醇脂肪酸在我们实验室合成。此前，我们报道了这些化合物相较于白藜芦醇改善的药学性质，包括在水中更好的溶解性以及与人血清白蛋白更紧密的结合。在此，我们研究白藜芦醇脂肪酸在Toll样受体2（TLR2）介导的细胞凋亡中的作用。我们发现白藜芦醇脂肪酸（R6A）显著抑制TLR2的表达。此外，在HEK293细胞中过表达TLR2导致R6A处理后细胞凋亡显著减少。而且，R6A对TLR2的抑制降低了血清剥夺所降低的磷酸化Akt和磷酸化糖原合酶激酶3β（GSK3β）的水平。因此，我们的研究表明白藜芦醇脂肪酸通过Akt/GSK3β途径参与TLR2抑制细胞凋亡。
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