GLUTATHIONE PROTECTION AGAINST HYPEROXIC INJURY IN LUNG

谷胱甘肽对肺部高氧损伤的保护作用

基本信息

批准号：
2219473
负责人：
Dean Paul Jones
金额：
$ 15.31万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-03-01 至 1995-06-30
项目状态：
已结题

项目摘要

DESCRIPTION: (Adapted from the applicant's abstract.) Pulmonary surfactant is a complex that reduces surface tension at the air-liquid interface and plays a crucial role in neonatal adaptation. A lack of surfactant, usually due to immaturity of the lung, leads to decreased pulmonary compliance and respiratory distress. The mainstay in the management of respiratory distress is oxygen and respiratory support. Oxidative injury from the treatment itself can lead to further pulmonary disease. The intracellular pool of glutathione provides protection against such injury because of its role in reduction of lipid peroxides, inhibition of free radical processes, and the removal of reactive electrophiles. Dr. Jones has found that pulmonary alveolar type II cells from adult and neonatal animals have a Na+-dependent transport system. This transport was demonstrated in healthy type II cells and the transport was demonstrated to be against a glutathione concentration gradient. This transport mechanism then allowed these cells to utilize exogenous glutathione for protection against oxidative injury. This protection by exogenous glutathione was in addition to that provided by endogenous pools of glutathione. The preliminary data have demonstrated that the lung can transport supplemental glutathione from the vasculature to the alveolar surface when ventilated under hyperoxic conditions. The purpose of this proposal is to characterize further the glutathione transport mechanisms that are involved in protection by exogenous glutathione. This will entail: 1) characterization of the mechanisms regulating glutathione transport by the alveolar type II cell, 2) examination of this transport system in plasma membrane vesicles obtained from alveolar type II cells and 3) isolation of the transporter as a prelude to studies of its properties and mechanism. The purification of the transporter will then be used for preparation of antibodies for investigations of the molecular biology of this system. The results of these studies may provide knowledge about pulmonary glutathione uptake and its function in protection against oxidative injury in alveolar type II cells.

描述：（改编自申请人的摘要。）肺表面活性物质是一种降低气液界面表面张力的复合物对新生儿的适应起着至关重要的作用。通常缺乏表面活性剂由于肺的不成熟，导致肺顺应性下降呼吸窘迫。呼吸管理的中流砥柱遇险时需要氧气和呼吸支持。氧化损伤来自治疗本身可能导致进一步的肺部疾病。细胞内的谷胱甘肽库可以防止此类伤害，因为它减少脂质过氧化物、抑制自由基过程的作用，以及反应性亲电子试剂的去除。琼斯博士发现来自成年和新生动物的肺泡 II 型细胞具有 Na+依赖的运输系统。这种运输在健康中得到了证明 II 型细胞和运输被证明是反对谷胱甘肽浓度梯度。然后这种传输机制允许这些细胞利用外源谷胱甘肽来防止氧化损伤。另外，外源性谷胱甘肽的这种保护作用内源性谷胱甘肽池提供的能量。初步数据已经证明肺可以运输补充的谷胱甘肽在高氧条件下通气时，脉管系统通向肺泡表面状况。该提案的目的是进一步描述参与保护的谷胱甘肽转运机制外源性谷胱甘肽。这将需要：1）表征 II 型肺泡细胞调节谷胱甘肽转运的机制， 2) 检查质膜囊泡中的运输系统从 II 型肺泡细胞获得，3) 转运蛋白的分离其性质和机制研究的前奏。的纯化然后转运蛋白将用于制备抗体该系统的分子生物学研究。结果这些研究可能提供有关肺谷胱甘肽摄取和其在保护 II 型肺泡氧化损伤中的作用细胞。