AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 3 285-L292, Copyright © 1995 by American Physiological Society
Glutathione homeostasis in alveolar epithelial cells in vitro and lung in vivo under oxidative stress
I. Rahman, X. Y. Li, K. Donaldson, D. J. Harrison and W. MacNee
Rayne Laboratory, Department of Medicine, University of Edinburgh, United Kingdom.
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.
