title: Glutathione homeostasis in alveolar epithelial cells in vitro and lung in vivo under oxidative stress.
abstract: We studied the acute effects of cigarette smoke condensate (CSC), H2O2, and tumor necrosis factor (TNF)-alpha on the glutathione (GSH) redox system in a human type II epithelial cell line (A549) in vitro. CSC, in vitro and in vivo after intratracheal instillation of CSC in the rat, produced a depletion of intracellular soluble GSH, concomitant with GSH-conjugate formation, without significant elevation of oxidized GSH (GSSG), protein-GSH mixed disulfides (PrSSG), nor any GSH efflux from the cells. By contrast, H2O2 (500 microM) after 5-min exposure to A549 cells caused significant depletion of intracellular GSH associated with an efflux of GSSG and a significant increase in the formation of PrSSG. TNF-alpha, in concentrations of 100 U/ml and 1,000 U/ml, produced a significant depletion of GSH in A549 cells after 4- and 24-h exposure, with an associated elevation of GSSG. The activities of glutathione peroxidase, gamma-glutamylcysteine synthetase, and glucose-6-phosphate dehydrogenase were significantly decreased in epithelial cells and in rat lungs after CSC exposure, without change in glutathione S-transferase and glutathione reductase activities. By contrast, H2O2 and TNF-alpha did not alter these enzyme activities in epithelial cells. Thus GSH depletion and alteration in enzyme activities in alveolar epithelial cells by CSC, H2O2, and TNF-alpha occur by different mechanisms.
authors.affiliation: Rayne Laboratory, Department of Medicine, University of Edinburgh, United Kingdom.
authors.forename: I
authors.initials: I
authors.lastname: Rahman
authors.forename: X Y
authors.initials: XY
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Donaldson
authors.forename: D J
authors.initials: DJ
authors.lastname: Harrison
authors.forename: W
authors.initials: W
authors.lastname: MacNee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004798:Enzymes / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010947:Plants, Toxic; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012906:Smoke; D014026:Nicotiana; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D004798:Enzymes; D012906:Smoke; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D005978:Glutathione; D019803:Glutathione Disulfide