COLLABORATIVE PROJECTS IN ENVIRONMENTAL HEALTH SCIENCES

环境健康科学合作项目

• 批准号: 5202202
• 负责人: K B TOMER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5202202
• 关键词: adduct; arachidonate; biological products; chemical structure function; cytochrome c; electron spin resonance spectroscopy; environmental health; free radicals; hemoprotein; human subject; ligands; mass spectrometry; myoglobin; oxidation; protein structure function; receptor; retinoate

This project includes those projects in which the mass spectrometry workgroup collaborates with other groups, within and without the Institute to solve problems of mutual interest. The major focuses of these projects are: 1) structure determination of unknown compounds; 2) identification and/or confirmation of biological pathways; 3) quantitation; and 4) development of strategies for the structure determination of biologically important compounds. Current collaborative projects under way include; 1) identification of ligands for orphan receptors (C. Weinberger, LRDT); 2) quantitation of arachidonic acid metabolites (D. Zeldin, LPP), and 3) mass spectrometric identification of spin-trapped free radicals (R. Mason, LMB). The project descriptions below demonstrate the wide variety of projects in which mass spectrometry can play an integral role. Orphan Receptors - We are supporting Dr. Weinberger's research into identifying native ligands to 'orphan receptors', receptors whose physiological role is unclear. The present project is the identification of retinoic acid X receptor, RXR. Quantitation of Arachidonic Acid Metabolites - The most sensitive and accurate method for quantitation of eicosanoids in physiological samples is by selected ion monitoring (SIM) under negative ion chemical ionization(NICI) mass spectrometry. We are currently quantifying epoxy- and dihydroxy-eicosatrienoic acids. The quanitation of epoxy eicosanoids is part of a study identifying formation of these compounds for the first time in human heart and identification of the protein regulating that formation. Identification of Spin-Trapped Free Radicals - Our major effort in this area has been the development and application of on-line LC/EPR/MS capabilities. We were the first group (and still one of only two groups) to successfully couple these techniques. Our current work in this area is the identification of spin adducts of cytochrome c and myoglobin. Oxidation radical formation of these hemeproteins maybe implicated on on aging, cancer and myocardial ischemia.

这个项目包括那些项目，其中质谱 与其他团体合作，内部和外部 学会解决共同关心的问题。 的主要焦点 这些项目是：1）未知化合物的结构测定; 2） 生物学途径的鉴定和/或确认; 3） 定量;和4）发展战略的结构 生物重要化合物的测定。 当前协作 正在进行的项目包括：1）确定孤儿配体 受体（C. Weinberger，LRDT）; 2）花生四烯酸的定量 代谢物（D. Zeldin，LPP）和3）质谱鉴定 自旋捕获自由基（R. Mason，LMB）。 项目说明 下面展示了各种各样的项目，其中质谱 可以发挥重要作用。 孤儿接待员-我们支持博士。 温伯格的研究，以确定天然配体的孤儿 受体，受体的生理作用尚不清楚。 本 本课题是鉴定维甲酸X受体（retinoicacidXreceptor，RXR）。 花生四烯酸蛋氨酸的定量-最灵敏， 生理样品中类二十烷酸的精确定量方法 是通过选择离子监测（SIM）在负离子化学 离子化（NICI）质谱。 我们目前正在量化环氧树脂- 和二羟基-二十碳三烯酸。 环氧类二十烷酸的定量 是一项研究的一部分， 人心脏中的时间和鉴定调节该时间的蛋白质， 阵 自旋捕获自由基的鉴定-我们的主要 在这方面的努力一直是发展和应用在线 LC/EPR/MS能力。 我们是第一批（也是唯一一批） 两组），以成功地结合这些技术。我们目前在 该领域是细胞色素c的自旋加合物的鉴定， 肌红蛋白这些血红素蛋白的氧化自由基形成可能 与衰老、癌症和心肌缺血有关