LYSOSMAL PROTEASES, PROTEIN TURNOVER AND AGING

溶酶体蛋白酶、蛋白质周转和衰老

• 批准号: 3114488
• 负责人: LEWIS A JACOBSON
• 金额: $ 8.88万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-12-01 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3114488
• 关键词: affinity chromatography; aging; electron microscopy; gene expression; high performance liquid chromatography; longevity; lysosomes; molecular cloning; mutagen testing; peptidases; protease inhibitor; proteolysis; radiotracer; spectrometry; temperature sensitive mutant

We propose to test the hypothesis that the rate of protein turnover declines with age, and that this leads to an accumulation of altered proteins. As a model organism, we are using the soil nematode Caenorhabditis elegans. We have already purified Cathepsin D, and now propose to purify and characterize lysosomal Cathepsin L. We will isolate mutants, both deficient and hyperproducing, affecting both of these proteases, and use them to determine the role of individual proteases in protein turnover, both of global protein and of specific test proteins. we are also designing delivery systems for protease inhibitors, so that these can be used to confirm results obtaine with mutants. Finally, we will assess the changes in the rate of protein turnover which occur during aging, and determine whether modulation of protease activity and/or protein turnover in vivo affects the rate of aging of C. elegans, using a multiparametric index of senescence.

我们建议检验蛋白质周转率的假设 随着年龄的增长而下降，这导致了变化的积累 蛋白质。 作为模型生物，我们使用的是土壤线虫 秀丽隐杆线虫。 我们已经纯化了组织蛋白酶D，现在 建议纯化和表征溶酶体组织蛋白酶L.我们将分离 不足和过度产生的突变体都影响了这两种突变体 蛋白酶，并使用它们来确定单个蛋白酶在 蛋白质更新，包括全球蛋白质和特定的测试蛋白。 我们 还在设计蛋白酶抑制剂的输送系统，以便这些 可用于确认突变体获得的结果。 最后，我们会的 评估在此期间发生的蛋白质周转率的变化 衰老，并确定蛋白酶活性和/或蛋白质的调节是否 体内营业额会影响秀丽隐杆线虫的衰老率 衰老的多参数指数。