Immunology and Molecular Medicine Laboratory, Department of Life Science, National Institute of Technology Rourkela, Odisha 769008, India.
ACS Appl Mater Interfaces. 2016 Nov 9;8(44):30005-30016. doi: 10.1021/acsami.6b10639. Epub 2016 Oct 26.
Advanced glycation end-products (AGEs) that result from nonenzymatic glycation are one of the major factors involved in diabetes and its secondary complications and diseases. This necessitates our urge to discover new compounds that may be used as potential AGEs inhibitors without affecting the normal structure and function of biomolecules. In the present study, we investigated the inhibitory effects of AgNP (silver nanoparticles) on AGEs formation as well as their inhibitory effects on glycation mediated cell toxicity via reactive oxygen species (ROS) production and DNA damage. The excitation-emission fluorescence spectroscopy was employed to investigate the interaction of AgNP during glycation. The values of conditional stability constant (log K = 4.44) derived from the Stern-Volmer equation indicate that AgNP have strong binding capacity for glycated protein. UV-vis, fluorescence, and Fourier transform infrared spectral data reveal complexation of AgNP with glycated bovine serum albumin, which significantly inhibits AGEs formation in a concentration-dependent manner. Cytotoxic evaluations suggest that simultaneous administration of AgNP and glycated product reduces cell death (42.82% ± 3.54) as compared to the glycated product alone. Similarly, ROS production in AgNP treated cells is significantly less compared to only glycated product treated cells. Although DNA damage studies show DNA damage in both GP and GP-AgNP treated cells, fluorescence activated cell sorting analysis demonstrates that glycated products induce cell death by necrosis, while AgNP cause cell death via apoptotic pathways. AgNP have a positive effect on restoring native protein structure deduced from spectral studies, and hence, inferences can be drawn that AgNP have ameliorating effects on glycated induced cytotoxicity observed in osteogenic Saos-2 cells.
非酶糖基化产生的晚期糖基化终产物(AGEs)是糖尿病及其继发并发症和疾病的主要因素之一。这就要求我们迫切需要发现新的化合物,这些化合物可以作为潜在的 AGEs 抑制剂使用,而不会影响生物分子的正常结构和功能。在本研究中,我们研究了 AgNP(银纳米粒子)对 AGEs 形成的抑制作用,以及通过活性氧(ROS)产生和 DNA 损伤对糖基化介导的细胞毒性的抑制作用。利用激发-发射荧光光谱法研究了 AgNP 在糖基化过程中的相互作用。Stem-Volmer 方程得出的条件稳定常数(log K = 4.44)值表明,AgNP 对糖基化蛋白具有很强的结合能力。紫外-可见、荧光和傅里叶变换红外光谱数据表明,AgNP 与糖基化牛血清白蛋白发生络合,AgNP 以浓度依赖的方式显著抑制 AGEs 的形成。细胞毒性评估表明,与单独的糖基化产物相比,同时给予 AgNP 和糖基化产物可降低细胞死亡(42.82%±3.54)。同样,与仅用糖基化产物处理的细胞相比,AgNP 处理的细胞中 ROS 的产生明显减少。尽管 DNA 损伤研究显示 GP 和 GP-AgNP 处理的细胞均有 DNA 损伤,但荧光激活细胞分选分析表明,糖基化产物通过坏死诱导细胞死亡,而 AgNP 通过凋亡途径导致细胞死亡。AgNP 对恢复光谱研究中天然蛋白结构有积极影响,因此可以推断,AgNP 对成骨 Saos-2 细胞中观察到的糖基化诱导的细胞毒性有改善作用。