ROLE OF PROTEIN METHYLATION IN CATARACT FORMATION

蛋白质甲基化在白内障形成中的作用

• 批准号: 3259606
• 负责人: STEVEN G CLARKE
• 金额: $ 6.76万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3259606
• 关键词: aging; biological information processing; cataract; chromatography; electrophoresis; human tissue; lens proteins; methyltransferase; radioassay

We propose to investigate the role of protein carboxyl methylation in cow and human eye lens function. We will focus on the possibility that this reaction (or the loss thereof) may be a molecular basis of cataractogenesis. We have recently shown that D-aspartyl residues are enzymatically methylated in human erythrocyte membrane and cytoskeletal proteins. This modification of aspartyl residues with abnormal stereoconfiguration by erythrocyte protein carboxyl methyltransferase may be a step in a protein repair pathway in these cells. Since D-aspartate has been found to accumulate in human lens proteins, and since lenses with brunescent cataracts (but not yellow cataracts) contain exceptionally high levels of D-aspartyl residues, we suspect that if the lens contains a similar protein repair pathway, then it loses efficiency with age and during certain forms of cataract development. Our preliminary results have indicated that, indeed, cow and human lenses contain protein carboxyl methyltransferase activity similar to that in the erythrocyte. We have also found that lenses with brunescent cataracts are highly deficient in this activity compared to that in normal lenses or lenses with yellow cataracts. We now intend to characterize the protein carboxyl methyltransferase in bovine lenses and in normal and cataractous human lenses. We will determine which proteins are methylated in these different lenses, and will be especially interested in the comparison between methyl acceptor proteins in normal and cataractous lenses. We will define the function and regulation of the protein carboxyl methylation pathway in normal lenses and will thus determine whether the failure of this pathway to function can affect the course of aging and cataract development in human lenses.

本研究旨在探讨蛋白质羧基甲基化在奶牛 和人眼透镜功能。 我们将关注的可能性， 反应（或其损失）可能是分子基础， 白内障形成 我们最近已经表明，D-乙酰基残基是 人红细胞膜和细胞骨架酶促甲基化 proteins. 这种修饰的乙酰基残基与异常 通过红细胞蛋白羧基甲基转移酶立体构型可以 是这些细胞中蛋白质修复途径的一个步骤。 由于D-天冬氨酸 已经发现在人的透镜蛋白中积累，并且由于具有 褐色白内障（但不是黄色白内障）含有异常高的 我们怀疑如果透镜中含有 类似的蛋白质修复途径，那么它会随着年龄的增长而失去效率， 在某些形式的白内障发展过程中。 我们的初步结果显示 研究表明，牛和人类的晶状体中确实含有蛋白质羧基 甲基转移酶活性与红细胞中的类似。 我们有 还发现，患有褐变白内障的晶状体高度缺乏 这种活性与正常晶状体或具有黄色的晶状体相比， 白内障 我们现在打算表征蛋白质羧基 牛晶状体和正常人及白内障患者晶状体中的甲基转移酶 眼镜. 我们将确定哪些蛋白质是甲基化在这些不同的 镜头，并将特别感兴趣的比较甲基之间 正常和白内障晶状体中的受体蛋白。 我们将定义 蛋白质羧基甲基化途径的功能和调控 正常的晶状体，并将因此确定是否失败，这一途径 功能可以影响衰老过程和白内障的发展， 人类晶状体