Wei Wei, Li Langen, Zhang Yufeng, Yang Jia, Zhang Yanmei, Xing Yiqiao
Department of Ophthalmology, Inner Mongolia People's Hospital, 20 Zhaowuda Road, Hohhot, Inner Mongolia 010017, China.
Department of Neurology, the Affiliated Hospital of Inner Mongolia Medical University, 1 Tongdao North Road, Hohhot, Inner Mongolia 010050, China.
ScientificWorldJournal. 2014;2014:750634. doi: 10.1155/2014/750634. Epub 2014 Jul 22.
The purpose was to investigate the protective effects of Vitamin C (Vit C) and the regulatory mechanism between Vit C and sirtuin 1 (SIRT1) in PREs during oxidative stress as Vit C and SIRT1 exerted famous effects as antioxidants. We found that moderate Vit C (100 µM) prevented ARPE-19 cells from damages induced by H2O2, including increasing viability, reducing apoptosis, and attenuating intracellular ROS levels. But lower and higher concentration of Vit C had no effects. Further results indicated that Vit C caused the dysregulation of some stress responses factors (SIRT1, p53 and FOXO3) in ARPE-19 cells response to H2O2. Moreover we found that SIRT1 activator resveratrol (SRV) stimulated significantly the protective effects of moderate Vit C, provided the property of antioxidative stress for the lower and higher concentration of Vit C in ARPE-19 cells as well. Consistently, nicotinamide (NA) relieved the protective functions of moderate Vit C. Interestingly, data also revealed the dysregulation of p53 and FOXO3 was dependent on the regulation of SIRT1 rather than Vit C. Summarily, the protective effect of Vit C against oxidative stress was involved in regulation of SIRT1. It suggested that combined application of Vit C and RSV might be a promising therapeutic method for AMD.
目的是研究维生素C(Vit C)的保护作用以及在氧化应激期间Vit C与沉默调节蛋白1(SIRT1)之间的调节机制,因为Vit C和SIRT1作为抗氧化剂发挥着显著作用。我们发现适度浓度的Vit C(100 μM)可防止ARPE - 19细胞受到H2O2诱导的损伤,包括提高细胞活力、减少细胞凋亡以及降低细胞内活性氧水平。但较低和较高浓度的Vit C则无此作用。进一步的结果表明,Vit C导致ARPE - 19细胞在对H2O2反应时一些应激反应因子(SIRT1、p53和FOXO3)的失调。此外,我们发现SIRT1激活剂白藜芦醇(SRV)显著增强了适度浓度Vit C的保护作用,同时也为ARPE - 19细胞中较低和较高浓度的Vit C提供了抗氧化应激的特性。同样,烟酰胺(NA)减弱了适度浓度Vit C的保护功能。有趣的是,数据还显示p53和FOXO3的失调依赖于SIRT1的调节而非Vit C的调节。总之,Vit C对氧化应激的保护作用涉及SIRT1的调节。这表明联合应用Vit C和白藜芦醇可能是治疗年龄相关性黄斑变性的一种有前景的治疗方法。