LENS PROTEINS: CHANGES DUE TO CATARACTOGENIC AGENTS

长期目标是：（a）阐明具体的结构特征 透镜中的单个晶体蛋白及其相互作用 其在普通透镜中产生透明结构，以及（B） 了解镜片在以下情况下变得不透明的原因和机制 白内障形成。 在本项目期间，研究将侧重于确定 负责蛋白质-蛋白质聚集的因子，蛋白质 修饰，并增加了超分子组织的稳定性 在正常透镜中，以及蛋白质结构不稳定的机制 在白内障形成过程中。 具体目标是： (1)为了确定蛋白质-蛋白质相互作用的机制， 在正常衰老和白内障发生中的聚集和不溶解。 研究包括单个晶体蛋白的结构和稳定性 牛和人的透镜。 (2)定义负责蛋白质修饰的因素，例如 人透镜中的色素沉着、不溶解和聚集。 完整 将研究年轻人、老年人和白内障人透镜， 了解蛋白质修饰的机制。 此外，镜片 如上所述，将研究来自印度和美国的 在不同环境条件下（例如， 饮食习惯和营养不良。 (3)目的：研究透镜蛋白质的结构变化， 糖化、氨甲酰化和Ca 2+离子。 除了适当的化学、生物化学和光谱分析外， 吸收、荧光和圆二色性（CD）等技术， 该项目还将使用高分辨率核磁共振（NMR）， 差示扫描量热法（DSC）和核磁弛豫 分散（NMRD）技术来实现目标。

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.