Regulation of Protein Synthesis and Degradation During Invertebrate Quiescence

无脊椎动物静止期间蛋白质合成和降解的调节

• 批准号: 9306652
• 负责人: Steven Hand
• 金额: $ 32万
• 依托单位: University of Colorado at Boulder
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9306652&HistoricalAwards=false
• 关键词: Regulation; Protein; Synthesis; Degradation; During

9306652 Hand This work will investigate how certain cells and tissues are able to survive long periods of time in dormant state, where energy metabolism and development are shutdown. Shrimp embryos (Artemia franciscana)are the focus of the outlined experiments, because their remarkable capacity to survive dormancy for months and even years is well known. For any dormant state, there are two problems that must be solved if an organisms is to tolerate bouts of quiescence. First, there must be a coordinated suppression of both energy use and energy production. Second, the integrity of macromolecules must be preserved during this period when little energy is available for their replacement or repair. Previous work with these embryos suggests that one cellular signal may be involved in mediating both of these phenomena. The first goal of the work is to explain how an energy consuming process like the synthesis of protein is indeed shutdown. The relative effect of limiting the copies of message (i.e., messenger RNA) that direct the cell to synthesize proteins, versus actually inhibiting the machinery itself (ribosomes) that builds the proteins will be compared. Finally, since synthesis is in some way suppressed during dormancy, then the rate of protein degradation must also be arrested in order to avoid depletion of macromolecules. Therefore, the second aim is to understand how degradation of protein (a normal process in an active cell)is reduced. Explaining how proteins are preserved during dormancy (in effect, placed into suspended animation) should provide insights that will be useful for other biological systems where survival depends on successful recovery from physical and chemical insults. The mechanisms by which cells can withstand long bouts of quiescence are apt to have important implications for numerous cases where metabolism is unavoidably suppressed or disrupted-- organ tissue transplantation, acute blockage of blood flow to tissues, and oxygen deprivation. ***

9306652手 这项工作将研究某些细胞和组织如何能够在休眠状态下存活很长一段时间，在休眠状态下，能量代谢和发育被关闭。虾胚胎（卤虫franciscana）是概述实验的重点，因为它们在休眠期存活数月甚至数年的非凡能力是众所周知的。 对于任何休眠状态，如果生物体要忍受间歇性的静止，就必须解决两个问题。首先，必须协调地抑制能源使用和能源生产。第二，在这段时间内，当几乎没有能量可供替换或修复时，必须保持大分子的完整性。先前对这些胚胎的研究表明，一种细胞信号可能参与介导这两种现象。 这项工作的第一个目标是解释像蛋白质合成这样的耗能过程是如何被关闭的。限制信息副本的相对效果（即， 信使RNA），指导细胞合成蛋白质，与实际上抑制机器本身（核糖体），建立蛋白质将进行比较。最后，由于合成在休眠期间以某种方式受到抑制，因此蛋白质降解的速率也必须被阻止，以避免大分子的耗尽。因此，第二个目的是了解蛋白质的降解（活性细胞中的正常过程）是如何减少的。 解释蛋白质如何在休眠期间保存（实际上，处于假死状态）应该提供对其他生物系统有用的见解，这些生物系统的生存取决于从物理和化学损伤中成功恢复。细胞能够承受长时间静止的机制，对于许多新陈代谢被抑制或破坏的情况，如器官组织移植、组织血流急性阻塞和缺氧，都有重要的意义。 ***