CAREER: Protein Metabolism During Mammalian Hibernation

职业：哺乳动物冬眠期间的蛋白质代谢

• 批准号: 0448396
• 负责人: Frank van Breukelen
• 金额: $ 74.5万
• 依托单位: University of Nevada Las Vegas
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0448396&HistoricalAwards=false
• 关键词: CAREER; Protein; Metabolism; During; Mammalian

During hibernation in ground squirrels, core body temperatures may be as low as -2 degrees C, heart rates may fall from around 200-250 beats per minute to as low as 3-4 erratic beats per minute, and metabolic rates can approach 1/100th of normal rates. The amazing metabolic depression of hibernation means that critical metabolic activities like protein synthesis and degradation must be reversibly turned off. However, the maintenance of protein pools is required if one is to survive. Biochemical and molecular strategies will be employed to examine the mechanisms by which protein metabolism is depressed as well as the implications of that depression. This research will address specifically the mechanism of how the bulk of protein synthesis initiation is down-regulated during hibernation. Also studied will be the role of a novel mechanism of protein synthesis initiation that could promote the survivorship of hibernation by increasing the production of stress proteins. Finally, the mechanism of how protein degradation is depressed will be examined. This research will not only answer basic questions on how a fundamental process like protein metabolism can be depressed while still allowing for survivorship, but in addition, should provide insight for future applied efforts that exploit these natural lessons for human health therapies. For example, a better understanding of hibernation may have profound implications for designing therapies for cardiac dysfunction, muscle disuse atrophy, and kidney failure. Education at both undergraduate and graduate levels will be an integral part of this research. An outreach component of this grant will be a local, children's television show produced in conjunction with UNLV-TV entitled 'Desert Survivor'. This program will showcase the local flora and fauna and is designed to promote scientific literacy in the local elementary schools.

在冬眠期间，地松鼠的核心体温可能低至-2摄氏度，心率可能从每分钟200-250次左右下降到每分钟3-4次不稳定的心率，代谢率可能接近正常速率的1/100。冬眠中惊人的代谢抑制意味着蛋白质合成和降解等关键代谢活动必须被可逆地关闭。然而，如果要生存，蛋白质池的维护是必需的。将采用生化和分子策略来检查蛋白质代谢被抑制的机制以及这种抑制的含义。本研究将具体探讨冬眠期间蛋白质合成起始量下调的机制。还将研究一种新的蛋白质合成启动机制的作用，该机制可以通过增加应激蛋白的产生来促进冬眠的存活。最后，将探讨如何抑制蛋白质降解的机制。这项研究不仅将回答诸如蛋白质代谢这样的基本过程如何在被抑制的同时仍然允许生存的基本问题，而且还将为未来利用这些自然经验教训进行人类健康治疗的应用工作提供见解。例如，更好地了解冬眠可能对设计治疗心功能障碍、肌肉废用性萎缩和肾衰竭具有深远的意义。本科和研究生阶段的教育将是这项研究的一个组成部分。这笔赠款的一个外联部分将是与联合国志愿人员办事处-电视台联合制作一个题为“沙漠幸存者”的当地儿童电视节目。这个项目将展示当地的动植物，旨在提高当地小学的科学素养。