LENS PROTEINS: CHANGES DUE TO CATARACTOGENIC AGENTS

这项计划的具体目的有两个：(1)研究 晶体蛋白质在溶液中的三维结构(构象)，以及 (2)研究其化学性质和构象的变化 紫外线、糖等致白内障药物的应用 分子和钙离子。光谱方法，如吸收， 荧光和圆二色谱将用于构象 学习。生化技术，包括光散射和 沉淀平衡将被用于聚集或交联 学习。对构象和分子间的了解很少。 引起超分子的晶状体蛋白的相互作用 负责透明度的正常镜头的组织。任何变化 在蛋白质的三维结构中会造成损失 这种有组织的结构会导致混浊(白内障)。在老化和 在白内障的发生过程中，晶状体蛋白质经历了许多修饰， 包括色素沉着和聚集。在糖尿病白内障中， 晶状体中的糖含量很高。糖本身或其代谢物可能会导致 聚集导致白内障的形成。钙的水平也是 高度白内障晶状体。有人提出，紫外线 太阳光是导致年龄相关变化的一个因素。 晶状体蛋白和老年性白内障。因此，作为糖尿病和糖尿病的模型 老年性白内障，该项目计划调查变化在 晶状体蛋白体外应用时的理化性质 那些导致白内障的药物。这项提议的长期目标是 确定正常晶状体蛋白质的分子排列 为了透明，也为了定义晶状体的分子机制 白内障形成过程中的变化。

Specific aims of the project are twofold: (1) to study the three-dimensional structure (conformation) of lens protein in solution, and (2) to study changes in chemical properties and the conformation upon application of cataractogenic agents such as ultraviolet light, sugar molecules, and calcium ion. Spectroscopic methods such as absorption, fluroescence, and circular dichroism, will be used for conformational studies. Biochemical techniques, including light scattering and sedimentation equilibrium will be used for aggregation or crosslinking studies. Little is known of the conformation and intermolecular interactions of the lens proteins that give rise to the supramolecular organization of the normal lens responsible for transparency. Any change in the three-dimensional structure of the proteins can cause the loss of this organized structure and lead to opacity (cataract). During aging and cataractogenesis, lens proteins undergo a number of modifications, including pigmentation and aggregation. In a diabetic cataract, the level of sugar in the lens is high. Sugar itself or its metabolites can cause aggregation leading to cataract formation. The level of calcium is also high in the cataractous lens. It has been proposed that the ultraviolet light from the sunlight is one factor responsible for age-related changes of lens protein and senile cataract. Hence, as a model for diabetic and senile cataract, the project plans to investigate the changes in physicochemical properties of lens protein upon in vitro application of those cataractogenic agents. The long-term objective of this proposal is to define the molecular arrangements of normal lens proteins responsible for transparency and also to define a molecular mechanism for the lens changes during cataract formation.