Nie Rong-Zu, Zhu Wei, Peng Jin-Ming, Ge Zhen-Zhen, Li Chun-Mei
College of Food Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.
College of Food Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China; Key Laboratory of Environment Correlative Food Science, Huazhong Agricultural University, Ministry of Education, Wuhan, 430070, China.
Biochimie. 2016 Jun;125:204-12. doi: 10.1016/j.biochi.2016.03.011. Epub 2016 Apr 12.
Because fibrillary protein aggregates is regarded to be closely associated with many diseases such as Alzheimer's disease, diabetes, and Parkinson's disease, growing interest and researches have been focused on finding potential fibrillation inhibitors. In the present study, the inhibitory effects of epigallocatechin-3-gallate (EGCG) and A-type dimeric epigallocatechin-3-gallate (A-type EGCG dimer) on the formation of insulin fibrillation were compared by multi-dimensional approaches including thioflavin-T (ThT) fluorescence assay, 1-anilinonaphthalene-8-sulfonic (ANS) fluorescence assay, dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and circular dichroism (CD) spectroscopy. Our results confirmed that A-type EGCG dimer is a more potent inhibitor against the formation of bovine insulin amyloid fibril than EGCG. In addition, A-type EGCG dimer could not only inhibit insulin amyloid fibril formation, but also change the aggregation pathway and induce bovine insulin into amorphous aggregates. The results of the present study may provide a new guide on finding novel anti-amyloidogenic agents.
由于纤维状蛋白质聚集体被认为与许多疾病密切相关，如阿尔茨海默病、糖尿病和帕金森病，因此人们对寻找潜在的纤维化抑制剂的兴趣日益浓厚，相关研究也越来越多。在本研究中，通过硫黄素-T（ThT）荧光测定、1-苯胺基萘-8-磺酸（ANS）荧光测定、动态光散射（DLS）、透射电子显微镜（TEM）、傅里叶变换红外（FTIR）光谱和圆二色性（CD）光谱等多维方法，比较了表没食子儿茶素-3-没食子酸酯（EGCG）和A型二聚表没食子儿茶素-3-没食子酸酯（A型EGCG二聚体）对胰岛素纤维化形成的抑制作用。我们的结果证实，A型EGCG二聚体比EGCG对牛胰岛素淀粉样纤维的形成具有更强的抑制作用。此外，A型EGCG二聚体不仅可以抑制胰岛素淀粉样纤维的形成，还可以改变聚集途径并诱导牛胰岛素形成无定形聚集体。本研究结果可能为寻找新型抗淀粉样蛋白生成剂提供新的指导。
