LENS PROTEINS: CHANGES DUE TO CATARACTOGENIC AGENTS

该项目的具体目标有两个：（1）研究 溶液中透镜蛋白的三维结构（构象），和 (2)研究化学性质和构象的变化， 应用白内障发生剂如紫外线、糖 分子和钙离子。 光谱方法如吸收， 荧光和圆二色性，将用于构象分析。 问题研究 生物化学技术，包括光散射和 沉降平衡将用于聚集或交联 问题研究 很少有人知道的构象和分子间 透镜蛋白的相互作用产生超分子 负责透明度的正常透镜的组织。 任何变化 蛋白质三维结构中的蛋白质， 这种有组织的结构并导致不透明（白内障）。 在老化和 在白内障发生过程中，透镜蛋白经历了许多修饰， 包括色素沉着和聚集。 在糖尿病性白内障中， 透镜中的糖含量很高。 糖本身或其代谢产物会导致 聚集导致白内障形成。 钙的水平也是 在白内障透镜的上方。 有人提出紫外线 来自太阳的光线是导致年龄相关变化的一个因素 透镜蛋白与老年性白内障的关系。 因此，作为糖尿病和 老年性白内障，该项目计划调查的变化， 体外应用后透镜蛋白的理化性质 那些致白内障的药物 这项建议的长远目标是 以确定正常透镜蛋白的分子排列 并且还限定了透镜的分子机制 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.