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.

我们建议研究蛋白质羧甲基化在奶牛中的作用。 和人眼晶状体的功能。我们将重点关注这一可能性 反应(或其损失)可能是 白内障的发生。我们最近已经证明D-天冬氨酸残基是 人红细胞膜和细胞骨架中的酶甲基化 蛋白质。这种天冬氨酸残基的修饰具有异常 红细胞蛋白羧甲基转移酶的立体构型可能 是这些细胞中蛋白质修复途径中的一个步骤。由于D-天冬氨酸 已被发现在人类晶状体中积累蛋白质，自从带有 深色白内障(但不是黄色白内障)的含量极高。 D-天冬氨酸残基水平，我们怀疑如果晶状体中含有 相似的蛋白质修复途径，然后随着年龄和年龄的增长而失去效率 在某些形式的白内障发展过程中。我们的初步结果是 表明，奶牛和人类的晶状体确实含有蛋白质羧基 甲基转移酶的活性与红细胞中的类似。我们有 还发现，患有深色白内障的晶状体在 这一活动与正常晶状体或黄色晶状体的比较 白内障。我们现在打算表征蛋白质的羧基。 牛晶状体及正常人和白内障患者晶状体中的甲基转移酶 隐形眼镜。我们将确定哪些蛋白质在这些不同的 镜片，并将特别感兴趣的比较甲基 正常和白内障晶状体中的受体蛋白。我们将定义 蛋白质羧甲基化途径的功能与调控 从而将决定这一通路是否失效 TO功能可影响衰老和白内障的发展过程 人类的镜片。