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.
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