LENS PROTEINS: CHANGES DUE TO CATARACTOGENIC AGENTS

在衰老和白内障发生过程中，透镜蛋白质经历了一个 化学和物理修饰的数量，即， 聚集、色素沉着和不溶性 proteins. 据信构象变化与 这些过程。 迄今为止的调查表明， 光、钙离子、糖分子（糖尿病性白内障）等， 在这种蛋白质修饰的致病因素中， 最终可能导致白内障的形成。 我们的目标是： 1. 了解正常透镜的分子特征 蛋白质，并了解其修改的原因。 我们 将研究：（a）亚基的分子结构， α-和β-晶体蛋白;和（B）相互作用的性质 在透镜晶体蛋白中。 2. 描述应用后分子特征的变化 以下白内障发生剂：（a）光;（B）活性 （c）糖、糖的代谢物，以及 糖基化;（d）Ca 2 +;和（e）氨甲酰化。 3. 以类似方式研究完整晶状体。 对于模型研究，将使用牛晶状体。 研究将 扩展到人类晶状体，老年人和年轻人，正常人和白内障患者 (as可用）。 将通过凝胶色谱法常规分离透镜晶状体蛋白 并通过HPLC进行表征。 适当的化学，生物化学， 流体动力学和光谱技术将用于 监测构象方面及其变化。 这些包括 凝胶色谱，凝胶电泳，沉降 通过超浓缩，荧光，磷光， 圆二色性和拉曼共振光谱。

During aging and cataractogenesis, lens proteins undergo a number of chemical and physical modifications, namely, aggregation, pigmentation, and increased production of insoluble proteins. It is believed that conformational change is associated with these processes. Investigations to date have suggested that light, calcium ion, sugar molecules (in diabetic cataract), etc. are among the causative factors for this protein modification which may eventually lead to cataract formation. Our aims are: 1. To gain insight into the molecular features of normal lens proteins and to understand the cause of their modifications. We will investigate: (a) the molecular structure of the subunits of alpha- and beta crystallins; and (b) the nature of interactions among lens crystallins. 2. To describe changes in the molecular features upon application of the following cataractogenic agents: (a) light; (b) active species of oxygen; (c) sugar, metabolites of sugar, and glycosylation; (d) Ca2+; and (e) carbamylation. 3. To study intact lenses in a similar manner. For model studies, bovine lenses will be used. Studies will be extended to human lenses, old and young, normal and cataractous (as available). Lens crystallin will be isolated routinely by gel chromatography and characterized by HPLC. Appropriate chemical, biochemical, hydrodynamic, and spectroscopic techniques will be used to monitor conformational aspects and their changes. These include gel chromatography, gel electrophoresis, sedimentation equilibrium by ultracentrifuge, fluorescence, phosphorescence, circular dichroism and Raman resonance spectroscopy.