UF PASS: Regulation of exercise transducers

UF PASS：运动传感器的调节

• 批准号: 10341087
• 负责人: Karyn A Esser
• 金额: $ 43.48万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10341087
• 关键词: Acute; Age; Animal Model; Animals; Apoptosis; Autophagocytosis; Blood; Body Composition; Body Weight; Brain; Cells; Chemicals; Chronic Disease; Collection; Custom; Data; Data Collection; Databases; Dependovirus; Disease; Exercise; Exposure to; Female; Florida; Frequencies; Genes; Goals; Guidelines; Harvest; Health; Home; Human; Informatics; Ischemia; Kidney; Length; Libraries; Location; Maps; Methods; Modeling; Molecular; Monitor; Muscle; Muscle Cells; Neurons; Outcome; Oxidative Stress; Phase; Physical activity; Physiological; Protocols documentation; Quality Control; Rattus; Rattus norvegicus; Regulation; Reperfusion Therapy; Reporter; Running; Sampling; Scientist; Sepsis; Ships; Site; Skeletal Muscle; Small Interfering RNA; Stimulus; Stress; System; Techniques; Technology; Testing; Therapeutic; Time; Tissue Banks; Tissue Preservation; Tissues; Training; Training Programs; Transducers; United States National Institutes of Health; Universities; VO2max; Work; base; cohort; endoplasmic reticulum stress; endurance exercise; experimental study; expression vector; gain of function; genetic testing; high throughput screening; improved; in vivo evaluation; kidney cell; male; novel; overexpression; oxidant stress; phase 1 study; phase 2 study; physical model; pre-clinical; preconditioning; prevent; release factor; resistance exercise; response; screening; secondary outcome; strength training; stress tolerance; treadmill

Abstract Exercise is a powerful and pleiotropic physiological stimulus that helps prevent many chronic diseases and is used as a therapeutic for disease. While the beneficial effects of exercise are extensively acknowledged there is still very little understood about the molecular transducers of the systems-wide effects. The goal of this University of Florida Molecular Transducers of Physical Activity Preclinical Animal Study Sites application (UF PASS) is to conduct experiments in animals that will provide tissues/blood (i.e. biospecimens) to the Chemical Analysis Sites for identification of molecular transducers induced by defined models of physical activity from tissues that cannot be obtained from humans as well as to conduct mechanistic studies that can support screening of novel transducers to quickly move the field forward. In Phase 1, UF PASS proposes to collect biospecimens for the Chemical Analysis sites following endurance (run-training) or resistance exercise protocols on male and female Fischer 344xBrown Norway rats (F344-BN) at three different ages. To better capture the dynamics of the exercise/adaptation responses we propose to: 1) Collect biospecimens at 5 selected timepoints following an acute bout of exercise on naïve and trained rats; 2) Collect biospecimens following short duration training (after 5 bouts) and 3) Collect biospecimens following long-term (8 weeks) training. For Phase 2, our hypothesis is that factors released from muscle (i.e. myokines) are the molecular transducers that function throughout the system to improve the well-established stress tolerance. The goal of these studies will be to employ high throughput screening technologies to test up to 1500 myokines. We will then use secondary screening techniques to test 100 candidates from which we will select up to 3 candidates for in vivo testing. The results of the experiments in Aim 3 will provide molecular evidence identifying a set of transducers, released from muscle, that are necessary for exercise induced systemic health. The goals of the UF PASS will be pursued by the following Specific Aims: Specific Aim 1: Center Coordination Phase. Specific Aim 2: Phase 1 Studies. To perform endurance and resistance exercise using male and female F344BN rats at 3-4, 16-18, and 27-29 mo. Specific Aim 3: Phase 2 Studies. The goal in Aim 3 is to test myokines as the exercise transducers for improved stress tolerance.

摘要运动是一种强有力的多效性生理刺激，有助于预防许多慢性 疾病，并被用作治疗疾病。虽然锻炼的有益效果是广泛的 公认的是，仍然很少了解分子换能器的系统范围内的影响。 这项佛罗里达大学身体活动分子传感器临床前动物研究的目标是 研究中心申请（UF PASS）是在动物中进行实验，提供组织/血液（即 生物标本）的化学分析地点，以确定分子换能器诱导的定义 从人体组织中获得的身体活动模型， 机制研究，可以支持筛选新的换能器，以快速推动该领域的发展。 在第1阶段，UF PASS建议在耐久性之后为化学分析中心收集生物标本 雄性和雌性Fischer 344 xBrown Norway大鼠（F344-BN）的跑步训练或阻力运动方案 在三个不同的年龄。为了更好地捕捉运动/适应反应的动态，我们建议： 1)在对未经训练和训练的大鼠进行急性运动后的5个选定时间点收集生物标本; 2)在短时间训练后（5次比赛后）收集生物样本，以及3） 长期（8周）训练。 对于第二阶段，我们的假设是从肌肉释放的因子（即肌因子）是分子转换器 在整个系统中发挥作用，以提高公认的压力耐受性。这些研究的目的 将采用高通量筛选技术来测试多达1500种肌因子。然后我们将使用 二次筛选技术，以测试100名候选人，我们将从中选择最多3名候选人进行体内试验。 试验.目标3中的实验结果将提供识别一组换能器的分子证据， 从肌肉中释放，这是必要的运动引起的全身健康。UF PASS的目标将 应遵循以下具体目标： 具体目标1：中心协调阶段。 具体目标2：1期研究。使用男性和女性进行耐力和阻力锻炼 3-4、16-18和27-29月龄F344 BN大鼠。 具体目标3：2期研究。目标3的目标是测试肌因子作为运动传感器， 提高抗压能力。