CORE--ANALYTICAL

核心——分析

• 批准号: 6353560
• 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: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6353560
• 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.

直接测量活性物种或 目前，ARDS患者的氧化应激反应。一个主要的限制 用于测量活性物种的是它们在生物中的短暂半衰期 系统。由于活性物种修饰生物分子，例如 蛋白质、脂质和DNA，对修饰靶标的测量提供了 用于检测和量化它们的实验工具。蛋白 羰基是由氨基酸残基直接氧化或 不饱和化合物氧化形成的醛的共轭反应 脂类或糖。总体而言，血浆蛋白羰基表明形成了 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， 过氧硝酸酯与二氧化碳一起提供了必要的硝化剂， 解释了血浆蛋白3-硝基酪氨酸的形成。过氧硝酸酯是 由一氧化氮和一氧化氮的近扩散限制反应形成 超氧化物。尿异前列腺素是由反应性物种攻击产生的 花生四烯酸在脂质双分子层中的选择性和敏感性 是脂质过氧化的结果。因此，分析的主要功能是 化学核心(核心C)是测量修饰后的血浆水平 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 细胞裂解物、肺组织、灌流液和血浆 项目4.核心C还将作为中央处理、存储和 项目3中收集的样品的分发设施。 分析化学将设在环境研究所 医学。核心C的优势包括已建立的协议 临床标本采集、加工、保存的体会 测量这些生物标志物的研究人员和 了解这些生物标记物的生化来源。