School of Biotechnology, Yeungnam University, Gyeongsan, 712-749, South Korea.
J Gerontol A Biol Sci Med Sci. 2011 Dec;66(12):1274-85. doi: 10.1093/gerona/glr169. Epub 2011 Sep 28.
Although rapamycin (rapa) is a fungicide, it is now believed to possess the capacity to extend mammalian life span. Because rapamycin is insoluble in water, its study in the aqueous phase has been limited. We therefore solubilized rapamycin in isotonic buffer using reconstituted high-density lipoprotein containing V156K-apolipoprotein A-I (V156K-rHDL). Rapamycin (final concentration, 0.1 mg/mL) was solubilized in rHDL containing either wild-type (WT) or V156K-apoA-I (1 mg/mL of protein) prepared using the sodium cholate dialysis method. V156K-rHDL containing rapamycin (V156K-rapa-rHDL) had a slightly larger particle size than rapamycin-loaded WT-rHDL (WT-rapa-rHDL). V156K-rapa-rHDL exhibited enhanced antioxidant ability, cholesteryl ester transfer protein inhibitory activity, and anti-atherosclerotic activity. Treatment with V156K-rapa-rHDL resulted in attenuation of senescence in human cells with increased cell survival and enhancement of tissue regenerative activities in zebrafish model compared with WT-rapa-rHDL or rHDL alone.
雷帕霉素（rapa）虽然是一种杀真菌剂，但现在被认为具有延长哺乳动物寿命的能力。由于雷帕霉素不溶于水，因此其在水相中的研究受到限制。我们因此使用含有 V156K-载脂蛋白 A-I（V156K-rHDL）的重组高密度脂蛋白（rHDL）将雷帕霉素溶解在等渗缓冲液中。雷帕霉素（终浓度为 0.1mg/mL）溶解在 rHDL 中，rHDL 中含有野生型（WT）或 V156K-apoA-I（蛋白浓度为 1mg/mL），这是使用胆酸钠透析法制备的。含有雷帕霉素的 V156K-rHDL（V156K-rapa-rHDL）的粒径略大于载有雷帕霉素的 WT-rHDL（WT-rapa-rHDL）。V156K-rapa-rHDL 表现出增强的抗氧化能力、胆固醇酯转移蛋白抑制活性和抗动脉粥样硬化活性。与 WT-rapa-rHDL 或 rHDL 单独处理相比，用 V156K-rapa-rHDL 处理导致人细胞衰老减弱，细胞存活率增加，并增强了斑马鱼模型中的组织再生活性。
