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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL039968-02
Application #
3357013
Study Section
Pathology A Study Section (PTHA)
Project Start
1988-03-01
Project End
1991-02-28
Budget Start
1989-03-01
Budget End
1990-02-28
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Dahm, L J; Jones, D P (2000) Rat jejunum controls luminal thiol-disulfide redox. J Nutr 130:2739-45
Chawla, R K; Watson, W H; Jones, D P (1996) Effect of hypoxia on hepatic DNA methylation and tRNA methyltransferase in rat: similarities to effects of methyl-deficient diets. J Cell Biochem 61:72-80
Bai, C; Jones, D P (1996) GSH transport and GSH-dependent detoxication in small intestine of rats exposed in vivo to hypoxia. Am J Physiol 271:G701-6
Jones, D P; Brown, L A; Sternberg, P (1995) Variability in glutathione-dependent detoxication in vivo and its relevance to detoxication of chemical mixtures. Toxicology 105:267-74
Dahm, L J; Jones, D P (1994) Clearance of glutathione disulfide from rat mesenteric vasculature. Toxicol Appl Pharmacol 129:272-82
Flagg, E W; Coates, R J; Eley, J W et al. (1994) Dietary glutathione intake in humans and the relationship between intake and plasma total glutathione level. Nutr Cancer 21:33-46
Chawla, R K; Jones, D P (1994) Abnormal metabolism of S-adenosyl-L-methionine in hypoxic rat liver. Similarities to its abnormal metabolism in alcoholic cirrhosis. Biochim Biophys Acta 1199:45-51
Bai, C; Brown, L A; Jones, D P (1994) Glutathione transport by type II cells in perfused rat lung. Am J Physiol 267:L447-55
Brown, L A (1994) Glutathione protects signal transduction in type II cells under oxidant stress. Am J Physiol 266:L172-7
Dahm, L J; Jones, D P (1994) Secretion of cysteine and glutathione from mucosa to lumen in rat small intestine. Am J Physiol 267:G292-300

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