AGING AND OXIDATION IN SKELETAL AND CARDIAC MUSCLE

骨骼肌和心肌的老化和氧化

• 批准号: 2442198
• 负责人: Diana Jean Bigelow
• 金额: $ 7.26万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2442198
• 关键词: aging; calcium flux; calcium transporting ATPase; cell senescence; cell type; chemical association; enzyme mechanism; enzyme structure; free radical oxygen; histochemistry /cytochemistry; laboratory rabbit; laboratory rat; membrane proteins; muscle cells; muscle relaxation; myocardium; oxidation; oxidative stress; peroxidation; phospholamban; phosphorylation; protein metabolism; sarcoplasmic reticulum; striated muscles; tissue /cell culture

The career goals of the candidate include building an internationally recognized independent research program in the area of active calcium transport and its relationship to the aging process. At the same time the candidate is interested in becoming a Full Professor at an academic institution. The candidate is currently an Assistant Professor at a major state university which has an excellent research environment with the exception of the heavy teaching load required of its faculty. Although her laboratory has demonstrated its ability to undertake first rate research, research progress is likely to be slowed by the excessive demands of non-research related activities on the candidate's time and energy. An Independent Scientist Award (ISA) would relieve this situation by substantially reducing the candidate's teaching and service responsibilities to a minimum in order to allow her to concentrate on research activities and to foster existing and new research collaborations during this crucial time in her research career development. The ISA is expected to significantly stimulate the candidate's research productivity and hence competitiveness for future funding. The proposed research addresses the mechanism and regulation of active calcium transport in sarcoplasmic reticulum (SR) membranes in both cardiac and fast twitch skeletal muscle, and how this process is affected by aging of the organism. Major research aims include: (1) identification of oxidative modifications to the Ca-ATPase and SR lipids initiated by exposure of isolated SR vesicles to reactive oxygen species, and if these simulate any of the observed age-related changes; (2) definition of the role of the cellular environment in modifying the susceptibility of SR membranes to oxidative conditions; (3) identification of age-related modifications, and associated structural and functional alterations of the Ca-ATPase and SR lipids in muscle; and (4) identification of the physical mechanism of phospholamban's regulation of the cardiac Ca- ATPase, and how this may be altered in aging or oxidative stress. These goals will involve an integrated approach to examining biochemical function and its relation to protein structure at the primary, secondary, tertiary and quartenary level.

候选人的职业目标包括建立一个国际 活性钙领域公认的独立研究计划 运输及其与衰老过程的关系。的同时 候选人有兴趣成为一个学术教授 机构。候选人目前是一个专业的助理教授 州立大学，具有良好的研究环境， 除了它的教师所需的沉重的教学负担。 虽然 她的实验室已经证明了它有能力承担第一流的 研究，研究进展可能会因过度 非研究相关活动对候选人时间的需求， 能源独立科学家奖（伊萨）将缓解这种情况 通过大幅减少候选人的教学和服务 为了让她能够集中精力 研究活动和促进现有的和新的研究 在她研究生涯的这一关键时期， 发展伊萨预计将大大刺激 候选人的研究生产力，从而为未来的竞争力 经费 该研究旨在探讨活性蛋白的作用机制和调控机制。 肌浆网（SR）膜中的钙转运 心脏和快速收缩骨骼肌，以及如何影响这一过程 通过有机体的老化。主要研究目标包括：（1）识别 对Ca-ATP酶和SR脂质的氧化修饰， 将分离的SR囊泡暴露于活性氧，如果这些 模拟任何观察到的年龄相关变化;（2）定义 细胞环境在改变SR易感性中的作用 膜的氧化条件;（3）识别年龄相关的 修饰以及相关的结构和功能改变， 肌肉中Ca-ATPase和SR脂质;（4）鉴定 受磷蛋白调节心肌钙离子的物理机制 ATP酶，以及它如何在衰老或氧化应激中改变。这些 目标将涉及一个综合的方法来检查生物化学 功能及其与蛋白质结构的关系， 三级和四级。