Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan.
Department of Optometry, Yuanpei University of Medical Technology, Hsinchu City 30015, Taiwan.
Spectrochim Acta A Mol Biomol Spectrosc. 2021 Nov 15;261:120023. doi: 10.1016/j.saa.2021.120023. Epub 2021 May 26.
Cataract is known as one of the leading causes of vision impairment worldwide. While the detailed mechanism of cataratogenesis remains unclear, cataract is believed to be correlated with the aggregation and/or misfolding of human ocular lens proteins called crystallins. A 173-residue structural protein human γD-crystallin is a major γ-crystallin protein in the human eye lens and associated with the development of juvenile and mature-onset cataracts. This work is aimed at investigating the effect of a small molecule, e.g., ortho-vanillin, on human γD-crystallin aggregation upon exposure to ultraviolet-C irradiation. According to the findings of right-angle light scattering, transmission electron microscopy, and gel electrophoresis, ortho-vanillin was demonstrated to dose-dependently suppress ultraviolet-C-triggered aggregation of human γD-crystallin. Results from the synchronous fluorescence spectroscopy, tryptophan fluorescence quenching, and molecular docking studies revealed the structural change of γD-crystallin induced by the interaction/binding between ortho-vanillin and protein. We believe the outcome from this work may contribute to the development of potential therapeutics for cataract.
白内障是全球范围内导致视力损害的主要原因之一。虽然白内障的发病机制尚不清楚，但白内障被认为与人类眼晶状体蛋白的聚集和/或错误折叠有关，这些蛋白被称为晶状体蛋白。173 个氨基酸残基的结构蛋白人γD-晶状体蛋白是人类眼晶状体中主要的γ-晶状体蛋白，与青少年型和成年型白内障的发展有关。本工作旨在研究小分子，如邻香草醛，对人γD-晶状体蛋白在暴露于紫外线-C 照射下聚集的影响。根据直角光散射、透射电子显微镜和凝胶电泳的结果，邻香草醛被证明能够剂量依赖性地抑制紫外线-C 触发的人γD-晶状体蛋白聚集。同步荧光光谱、色氨酸荧光猝灭和分子对接研究的结果表明，邻香草醛与蛋白质之间的相互作用/结合导致γD-晶状体蛋白的结构发生变化。我们相信这项工作的结果可能有助于开发白内障的潜在治疗方法。
