探討槲皮素對人類γD型水晶體蛋白在紫外光下 聚集行為之抑制作用

Exploring the Inhibiting Effect of Quercetin on the Aggregation Behavior of Human γD Crystallin under UV-C Irradiation

陳偉安(Wei-An Chen)

指導教授 ： 王勝仕

國立臺灣大學/工學院/化學工程學研究所/碩士(2014年)

https://doi.org/10.6342/NTU.2014.10089

摘要

白內障(Cataract)是由於水晶體蛋白(crystallins)聚集(aggregation)或沉澱而導致水晶體混濁(opacification)的一種疾病，同時也是全球致使失明的首要因素。過去研究指出，紫外光(ultraviolet，UV)的曝曬是引起年老性白內障(age-onset/senile cataract)之主要成因。透過ThT螢光、遠紫外線圓二色光譜學、蛋白質自身螢光、動態光散射、和穿透式電子顯微鏡等分析方法，本研究旨在探討人類γD型水晶體蛋白(Human γD crystallin，HγDC)於UV-C照射下的聚集行為及槲皮素(quercetin)對其之抑制作用，其中人類γD型水晶體蛋白是水晶體中為數眾多的結構性(structural)蛋白質，而榭皮素(quercetin)為廣泛分布於自然界中可食之抗氧化劑(antioxidant)。本研究結果顯示，人類γD型水晶體蛋白的聚集會隨照射時間而增多，且過程中伴隨著蛋白質之部分結構展開，此外，榭皮素抑制了UV-C誘導生成之聚集體的總量及其粒徑大小，此抑制效果與環境中所含榭皮素之濃度有高度正相關。相信本研究之成果將對於治療年老性白內障具潛力的藥物之設計及發展上應有所貢獻。

關鍵字

白內障 ； 人類γD型水晶體蛋白 ； 紫外線 ； 蛋白質聚集 ； 榭皮素

並列摘要

Cataract, the opacification of the eye lens due to aggregation and precipitation of crystallin proteins, is the leading cause of blindness worldwide. Evidence shows that exposure to ultraviolet (UV) is one of the major factors causing age-onset cataract. With ThT binding assay, far-UV circular dichroism spectroscopy, intrinsic (tryptophan) fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy, this research aims at examining the effects of quercetin, an edible antioxidant widely distributed in nature on aggregation behavior of human γD crystallin (HγDC), an abundant structural protein in lens, under UV-C irradiation. Our results demonstrated that the aggregation of HγDC was observed to be augmented upon irradiation dose, accompanied by solvent exposure. In addition, quercetin exhibits a concentration-dependently inhibitory action toward UV-C induced aggregation of HγDC in terms of the amonnt and size of aggregated species. We believe the outcome from this study may contribute to the design and development of potential therapeutics for senile cataract.

並列關鍵字

Cataract ； human γD crystallin(HγDC) ； protein aggregation ； quercetin ； UV-C

參考文獻

Reference

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