CORE--ANALYTICAL

核心——分析

• 批准号: 6202610
• 负责人: HARRY ISCHIROPOULOS
• 金额: $ 15.58万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6202610
• 关键词: analytical chemistry; biomedical facility; blood chemistry; free radical oxygen

Limited number of studies that directly measure reactive species or oxidative stress in patients with ARDS are presently. A major limitation for measuring reactive species is their short half life in biological systems. Since reactive species modify biological molecules such as proteins, lipids and DNA, measurement of the modified targets provide the experimental tools for their detection and quantification. Protein carbonyls are derived by the direct oxidation of amino acid residues or conjugation of aldehydes that are formed by the oxidation of unsaturated lipids or sugars. Overall plasma protein carbonyls indicate the formation of oxidants. Nitration of protein tyrosine residues results in the formation of 3-nitrotyrosine. Previous we found that the reaction of peroxynitrate with C02 provides the necessary nitrating agent that explains the formation of plasm protein 3-nitrotyrosine. Peroxynitrate is formed by the nearly diffusion limited reaction of nitric oxide and superoxide. Urinary isoprostanes are generated by reactive species attack on arachidonate in lipid bilayers and is selective and sensitive indicator of lipid peroxidation. Therefore, the main function of the analytical chemistry core (Core C) is to measure the levels of modified plasma proteins (carbonyls and 3-nitrotyrosine) and urinary isoprostanes in the human samples for Project 3. Protein carbonyls will be also measured in cell lysates, lung tissue, perfusate and plasma in samples generated in Project 4. Core C will also function as a central processing, storage and distribution facility for the samples collected in Project 3. The analytical chemistry will be located at the Institute for Environmental Medicine. Strengths of Core C include the established protocols for clinical specimen collection, processing and storage, the experience of the investigators with measuring these biological markers and the understanding of the biochemical origin of these biological markers.

直接测量活性物质或活性物质的研究数量有限 ARDS 患者的氧化应激状况目前尚不清楚。一个主要限制 用于测量活性物质的原因是它们在生物中的半衰期短 系统。由于活性物质会改变生物分子，例如 蛋白质、脂质和 DNA，对修饰目标的测量提供了 用于检测和定量的实验工具。蛋白质 羰基是通过氨基酸残基的直接氧化衍生的或 由不饱和化合物氧化形成的醛的共轭 脂质或糖。总血浆蛋白羰基表明形成 氧化剂。蛋白质酪氨酸残基的硝化导致 3-硝基酪氨酸的形成。之前我们发现反应 过氧硝酸盐与CO2提供必要的硝化剂 解释了血浆蛋白 3-硝基酪氨酸的形成。过氧硝酸盐是 由一氧化氮的近扩散限制反应形成 超氧化物。尿液中的异前列烷是由活性物质攻击产生的 脂双层中的花生四烯酸，是选择性和敏感的指示剂 脂质过氧化作用。因此，分析的主要功能 化学核心（核心 C）是测量改性等离子体的水平 蛋白质（羰基和 3-硝基酪氨酸）和尿中的异前列腺素 项目 3 的人体样本。蛋白质羰基也将在 样品中产生的细胞裂解物、肺组织、灌流液和血浆 项目 4. Core C 还将充当中央处理、存储和 项目 3 中收集的样本的分配设施。 分析化学将设在环境研究所 药品。 Core C 的优势包括已建立的协议 临床标本采集、处理和保存的经验 研究人员测量这些生物标志物 了解这些生物标记的生化起源。