H202 AND OXY-RADICAL STRESS IN CATECHOLAMINE NEURONS

儿茶酚胺神经元中的 H202 和氧自由基应激

• 批准号: 3405960
• 负责人: Gerald Cohen
• 金额: $ 21.37万
• 依托单位: MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-12-01 至 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3405960
• 关键词: MAO inhibitors; catecholamines; detoxification; electron microscopy; fluorescence microscopy; gas chromatography mass spectrometry; glutathione; high performance liquid chromatography; hydrogen peroxide; hydroxyl group; immunochemistry; neurons; neurotoxins; organ culture; stress; superoxides

The goals are to assess the production, reactions, and detoxification pathways of hydrogen peroxide and oxy-radicals within the nervous system. Experiments will concentrate on catecholamine neurons, which provide an arry of drug-mediated tools that facilitate manipulations in vitro and in vivo, and anatomical tools that permit the visualization of these neurons where they exist intermingled with other cell types. For example, catecholamine levels can be lowered (e.g., alpha-methyl-p-tyrosine) or raised (e.g., L-dopa), and monoamine neurons can be visualized under the fluorescence microscope or by electron microscopy. A major tool will be the investigation of neurotoxins that appear to operate via the formation of hydrogen peroxide and oxy-radicals. Organotypic cultures of nervous system will studied; experiments with animals are also planned. We are particularly interested in the role that monoamine oxidase may play as a primary generator of hydrogen peroxide within monoamine neurons. Hydrogen peroxide, in turn, serves as precursor of the highly-reactive hydroxyl radical. The immediate research goals are the amplification of experiments that are already under way. These include: 1) the study of the neurotoxin, MPTP; 2) histochemical evaluation of intracellular levels of GSH (reduced glutathione) as an index of oxidative stress; and 3) development of technology to detect the hydroxyl radical within catecholamine neurons. The long range goals are 1) to apply the new methodology to study other neurotoxins or other procedures that appear to produce an oxidative stress in the nervous system (e.g., hyperbaric oxygenation, ischemia, reperfusion stress) and 2) to evaluate other aspects of GSH metabolism that can provide an index of oxidative stress (study of GSSG, mixed disulfides, and GSH adducts with catecholamines). These studies will help to define the role of peroxides and oxy-radicals in damage to the nervous system.

目标是评估生产，反应和排毒 神经系统中过氧化氢和氧基的途径。 实验将集中在儿茶酚胺神经元上，该神经元提供 药物介导的工具的Arry，促进体外操纵和 体内和解剖工具允许可视化这些神经元 它们存在与其他细胞类型相结合。 例如， 可以降低儿茶酚胺水平（例如α-甲基-P-酪氨酸）或 可以在凸起的（例如L-DOPA）和单胺神经元下看到 荧光显微镜或通过电子显微镜。 主要工具将是 研究似乎通过形成作用的神经毒素的研究 过氧化氢和氧气自由基。 神经的器官文化 系统将研究；还计划进行动物实验。 我们是 对单胺氧化酶可能起作用的作用特别感兴趣 单胺神经元内过氧化氢的主要发生器。 氢 过氧化物又是高度反应性羟基的前体 激进的。 直接的研究目标是放大实验 已经开始。 其中包括：1）神经毒素MPTP的研究； 2）细胞内GSH的组织化学评估（降低 谷胱甘肽）作为氧化应激的指数； 3）发展 检测儿茶酚胺神经元内羟基自由基的技术。 远距离目标是1）应用新方法来研究其他方法 神经毒素或其他似乎产生氧化应激的程序 在神经系统中（例如，高压氧合，缺血，再灌注 压力）和2）评估可以提供GSH代谢的其他方面 氧化应激的指数（研究GSSG，混合二硫化物和GSH的指数 儿茶酚胺的加合物）。 这些研究将有助于定义角色 神经系统损害中的过氧化物和氧化物。