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.

我们建议研究蛋白羧甲基化在牛中的作用 和人眼镜透镜的功能。 我们将重点介绍这一可能性 反应（或其丢失）可能是分子基础 白内生生成。 我们最近表明D-冬冬基残基是 在人红细胞膜和细胞骨架中酶促甲基化 蛋白质。 这种异常的天冬氨酸残基的修饰 红细胞蛋白羧基甲基转移酶的立体配合可能 在这些细胞的蛋白质修复途径中迈出一步。 自D-天冬氨酸以来 已经发现在人透镜蛋白中积聚，并且由于具有 肥大性白内障（但不黄色白内障）包含异常高的白内障 D-冬冬基残基的水平，我们怀疑如果镜头包含A 类似的蛋白质修复途径，然后会随着年龄的增长而失去效率 在某些形式的白内障发育中。 我们的初步结果 表明确实，牛和人透镜含有蛋白质羧基 甲基转移酶的活性类似于红细胞。 我们有 还发现，具有刚牙白内障的镜片在高度缺乏 与普通镜头或黄色镜头相比 白内障。 我们现在打算表征蛋白质羧基 牛透镜中的甲基转移酶以及正常和白内障人 镜片。 我们将确定哪些蛋白在这些不同的 镜片，并且对甲基的比较特别感兴趣 正常和白内障镜片中的受体蛋白。 我们将定义 蛋白羧基甲基化途径的功能和调节 正常镜头，因此将确定该途径的故障是否 功能可以影响衰老和白内障发展的过程 人镜。