This proposed research will continue our investigations of factors which regulate lung glutathione (GSH) levels. GSH is an important antioxidant and is involved in protection against radiation, airborne pollutants and various toxins. We have also shown that GSH is important in protection of lungs against high concentrations of oxygen, such as those often administered to patients with compromised lung functions. There are natural mechanisms by which the lung and other organs can adapt to these stresses by increasing cell GSH concentrations. We will be investigating these mechanisms in two separate lung-derived cell model systems. We have found that endothelial cells and type II alveolar epithelial cells have very different mechanisms for regulating GSH levels. Endothelial cell GSH regulation in vitro depends on the availability of cystine and cysteine. Many oxidant stresses induce cystine transport. We will be studying the mechanisms of this induction by attempting to isolate and characterize the specific transport protein(s) for cystine. Type II cell GHS regulation in vitro is apparently not related to cystine transport. We will also be exploring transport of cystine and GSH into these cells. The combination of these studies should result in greater understanding of how whole lung GSH levels are regulated.
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