GLUTATHIONE PROTECTION AGAINST HYPEROXIC INJURY IN LUNG

谷胱甘肽对肺部高氧损伤的保护作用

• 批准号: 3357013
• 负责人: Dean Paul Jones
• 金额: $ 10.92万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3357013
• 关键词: adult respiratory distress syndrome; affinity chromatography; antioxidants; disease /disorder model; fluorescent dye /probe; glutathione; glutathione peroxidase; glutathione reductase; high performance liquid chromatography; histochemistry /cytochemistry; hormone regulation /control mechanism; hyperoxia; immunochemistry; laboratory rabbit; laboratory rat; membrane permeability; newborn animals; perfusion; protein structure; protein transport; pulmonary surfactants; radiotracer; respiratory distress syndrome of newborn; respiratory epithelium; respiratory pharmacology

Oxidative processes are involved in several clinically important conditions, such as in hyperoxic therapy of fetal and adult respiratory syndromes. The intracellular GSH pool provides protection against such injury because of its role in reduction of peroxides, inhibition of free radical processes, and removal of reactive elecrophiles. We recently found that alveolar type II cells have a Na+-dependent transport system that allows these cells to utilize exogenous GSH for protection against oxidative injury. The purpose of this proposal is to investigate the protection afforded by exogenous GSH against hyperoxic injury. This will entail 1) examination of effects of exogenous GSH on the responses to oxidative injury in lung in vivo, in isolated perfused lung and in alveolar type II cells, 2) characterization of distribution and properties of GSH transport systems in membrane of lung cells, and 3) isolation of the transporter as a prelude to studies of its properties and mechanism and to use for preparation of antibodies for investigations of the molecular biology of this system. The results of these studies will provide important new knowledge about GSH uptake in lung and its function in protection against oxidative injury. This will be of immediate value in the effort to improve therapeusis of oxidative injury in conditions such as hyaline membrane disease.

氧化过程涉及几个临床上重要的过程 条件，例如胎儿和成人的高氧治疗 呼吸系统综合症。 细胞内 GSH 池提供 防止这种伤害，因为它的作用是减少 过氧化物，抑制自由基过程，并去除 反应性亲电试剂。 我们最近发现 II 型肺泡 细胞有一个依赖Na+的运输系统，允许这些 细胞利用外源 GSH 来防止氧化 受伤。 本提案的目的是调查 外源性谷胱甘肽对高氧损伤具有保护作用。 这将需要 1) 检查外源 GSH 对 体内肺氧化损伤的反应，在分离灌注中 肺和肺泡 II 型细胞，2) 特征 谷胱甘肽转运系统在膜中的分布和特性 肺细胞，3) 转运蛋白的分离作为前奏 其性质、机理研究及其制备方法 用于研究该分子生物学的抗体 系统。 这些研究结果将提供重要的新 肺摄取GSH及其保护作用的知识 对抗氧化损伤。 这将具有立竿见影的价值 努力改善氧化损伤的治疗 如透明膜病。