Geroscience Redox Biology Core

老年科学氧化还原生物学核心

• 批准号: 10424602
• 负责人: HOLLY VAN REMMEN
• 金额: $ 18.68万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10424602
• 关键词: Age; Aging; Bioenergetics; Biological; Biological Assay; Biology; Biology of Aging; Blood Vessels; Cell Culture Techniques; Cell Respiration; Cells; Cellular Structures; Charge; Communities; Couples; DNA; Deoxyguanosine; Diabetes Mellitus; Diffusion Magnetic Resonance Imaging; Disease; Environment; Equilibrium; Equipment; Evaluation; Excision; F2-Isoprostanes; Free Radicals; Freezing; Fresh Tissue; Functional Magnetic Resonance Imaging; Generations; Genus Hippocampus; Geroscience; Glutathione Disulfide; Goals; Homeostasis; Human; Hydrogen; In Vitro; Individual; Institution; Invertebrates; Laboratories; Lipid Peroxidation; Lipids; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant Neoplasms; Measurement; Measures; Metabolism; Mitochondria; Modeling; Molecular; Mus; NADH; NADP; Nature; Neurodegenerative Disorders; Oklahoma; Organism; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxygen; Pathway interactions; Phosphorus; Physiological Processes; Process; Production; Proteins; Reactive Oxygen Species; Reproducibility; Research; Research Personnel; Respiration; Rodent; Sampling; Sensitivity and Specificity; Series; Services; Ships; Shock; Site; Spin Trapping; System; Tissues; Vascular Diseases; age related; cell injury; cost; energy balance; extracellular; free radical oxygen; in vivo; in vivo imaging; insight; oxidation; oxidative damage; perfusion imaging; prevent

The goal of the Geroscience Redox Biology Core is to provide investigators with a coordinated and comprehensive evaluation of the molecules, pathways, and systems that contribute to oxidative metabolism and oxidative stress. These analyses include state of the art accurate and sensitive measures of redox and energy balance as well as oxidative damage, reactive oxygen species production and mitochondrial function. Redox status and oxidant homeostasis have a major impact on physiologic processes. As a consequence, they contribute significantly to basic mechanisms of aging as well as a number of age-related diseases, and are key pathways in geroscience. The Specific Aims for this Core are the following: Specific Aim 1. To perform accurate and comprehensive analyses of redox status (GSH/GSSG, NADPH/NADP+, NADH/NAD+,), and oxidative stress and damage markers (lipid peroxidation, e.g., F2-isoprostanes; protein oxidation, e.g., carbonyls; and DNA oxidation, e.g. 8-oxo-deoxyguanosine). Redox and oxidative damage endpoints are present in limited amounts and may be unstable. The expertise in the Geroscience Redox Biology Core allows for these analyses to be performed with the highest possible sensitivity and accuracy. In addition, the analyses the Geroscience Redox Biology Core provides are especially appropriate for a Research Core because they require costly equipment and significant technologic expertise that prevents these types of analyses to routine measures in individual laboratories. Finally, because we are analyzing levels of highly specific biological compounds, our redox and oxidative damage assays can be applied to tissues or cells from any living organism. Specific Aim 2. To provide assays of mitochondrial function, energetic status, and reactive oxygen species generation using permeabilized tissue, isolated mitochondria, and cell culture models. Although these assays require fresh tissue/cells, we have successfully performed these services for investigators at external sites who can send us small numbers of mice. Specific Aim 3. To provide in vivo analyses of free radical production, we have expanded the capabilities of the Geroscience Redox Biology Core in this renewal to include in vivo analyses of redox and energy status, vascular dysfunction, and tissue structural changes. The Geroscience Redox Biology Core will now provide in vivo redox analyses of free radical levels and oxygen status using magnetic resonance imaging (MRI) and immuno-spin trapping (IST). In addition functional MRI (fMRI), will be used for oxygen status and energy status obtained from tissue-localized phosphorous (31P)- and hydrogen (1H)-MR spectroscopy. Overall, the Geroscience Redox Biology Core will provide a comprehensive panel of endpoint markers of redox balance and oxidative stress as well as measures of contributing factors such as mitochondrial function and free radical generation in vitro and in vivo that can impact many aspects of anging and Geroscience.

老年科学氧化还原生物学核心的目标是为研究人员提供一个协调的和 对参与氧化代谢的分子、途径和系统进行综合评估 氧化应激。这些分析包括最先进、准确和灵敏的氧化还原和能量测量。 平衡以及氧化损伤、活性氧的产生和线粒体功能。氧化还原 状态和氧化剂的动态平衡对生理过程有重要影响。因此，他们 对衰老的基本机制以及一些与年龄有关的疾病有重大贡献，并且是关键 老年科学中的途径。这一核心的具体目标如下：具体目标1.准确执行 以及氧化还原状态(GSH/GSSG、NADPH/NADP+、NADH/NAD+)和氧化应激的综合分析 和损伤标记物(脂质过氧化，例如F2-异前列烷；蛋白质氧化，例如，羰基；和DNA 氧化，如8-氧-脱氧鸟苷)。氧化还原和氧化损伤的终点是有限的 而且可能不稳定。Geroscience氧化还原生物学核心的专业知识使这些分析能够 以尽可能高的灵敏度和精确度执行。此外，对老年科学的氧化还原进行了分析 生物核心设备特别适用于研究核心，因为它们需要昂贵的设备 和重要的技术专业知识，防止这些类型的分析对个人的常规测量 实验室。最后，因为我们正在分析高度特定的生物化合物的水平，我们的氧化还原和 氧化损伤分析可以应用于任何活着的有机体的组织或细胞。具体目标2.提供 用通透性测定线粒体功能、能量状态和活性氧产生 组织、分离的线粒体和细胞培养模型。尽管这些分析需要新鲜的组织/细胞，但我们有 成功地为外部站点的调查人员提供了这些服务，他们可以给我们送来少量的老鼠。 具体目标3.为了提供体内自由基产生的分析，我们扩展了 这次更新的老年科学氧化还原生物学核心包括体内氧化还原和能量状态的分析，血管 功能障碍和组织结构改变。老年科学氧化还原生物学核心现在将提供体内氧化还原 磁共振成像和免疫自旋分析氧自由基水平和氧状态 陷阱(IST)。此外，功能磁共振成像(FMRI)将用于从以下位置获得的氧气状态和能量状态 组织定位的磷(31P)和氢(1H)-磁共振波谱。 总体而言，Geroscience氧化还原生物学核心将提供一套全面的终点标记 氧化还原平衡和氧化应激，以及线粒体功能等影响因素的测量 以及在体外和体内产生的自由基，可以影响钓鱼和老年科学的许多方面。