LENS PROTEINS: CHANGES DUE TO CATARACTOGENIC AGENTS

长期目标是：(A)阐明特定的结构特征 晶状体中的单个晶体蛋白以及它们之间的相互作用 在正常的镜片中产生透明结构，以及(B) 了解镜片变得不透明的原因和机制 白内障形成。在本项目期间，研究将集中在定义 蛋白质-蛋白质聚集的影响因素 修饰，并增加超分子组织的稳定性 在正常晶体中，以及蛋白质结构失稳的机制 在白内障形成过程中。具体目标是： (1)确定蛋白质-蛋白质相互作用导致 正常衰老和白内障发生中的聚集和不溶解。 研究包括分离的单个晶体蛋白的结构和稳定性 来自牛和人类的晶状体。 (2)界定影响蛋白质修饰的因素，例如 人类晶状体中的色素沉着、不溶解和聚集。完好无损 人类晶状体，年轻的，老年的和白内障的，将被调查 了解蛋白质修饰的机制。此外，镜片 如上所述，将对印度和美国的情况进行研究，以区分 不同环境条件下的蛋白质修饰(如 光)、食物习惯和营养不良。 (3)研究晶状体蛋白质的结构变化。 糖基化、氨甲基化和钙离子。 除了适当的化学、生物化学和光谱学 吸收、荧光和圆二色(CD)等技术， 该项目还将使用高分辨率核磁共振(核磁共振)， 差示扫描量热法(DSC)和核磁弛豫 分散(NMRD)技术来实现这些目标。

The long-term objectives are (a) to elucidate specific structural features of the individual crystallins in the lens and the interactions between them that give rise to a transparent structure in normal lenses, and (b) to understand the cause and mechanism by which lenses become opaque upon cataract formation. In this project period, studies will focus on defining the factors responsible for protein-protein aggregation, protein modifications, and increased stability in the supramolecular organization in normal lens, and the mechanism of destabilization of protein structure during cataractogenesis. The specific aims are: (1) To determine the mechanism of protein-protein interaction leading to aggregation and insolubilization in normal aging and cataractogenesis. Studies include structure and stability of individual crystallins isolated from bovine and human lens. (2) To define the factors responsible for protein modification, such as pigmentation, insolubilization, and aggregation in human lens. Intact human lens, young, aged, and cataractous, will be investigated to understand the mechanism of protein modifications. In addition, lenses from India and the US will be studied, as described above, to distinguish the protein modifications under different environmental conditions (such as light), food habits, and malnutrition. (3) To investigate the structural changes of lens proteins due to glycation, carbamylation, and Ca2+ ion. In addition to appropriate chemical, biochemical, and spectroscopic techniques such as absorption, fluorescence, and circular dichroism (CD), the project will also use high-resolution nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), and nuclear magnetic relaxation dispersion (NMRD) techniques to accomplish the aims.