APStracts 2:0079L, 1995.

Glutathione homeostasis in alveolar epithelial cells in vitro and lung in vivo under oxidative stress. I, Rahman, Li Xy, Donaldson K, Harrison Dj, Macnee W. The Rayne Laboratory, Respiratory Medicine Unit, Department of Medicine (RIE), and Pathology, University of Edinburgh and the Department of Biological Sciences, Napier University, Edinburgh, Scotland, UK

APStracts 2:0079L, 1995.

We studied the acute effects of cigarette smoke condensate (CSC), H2O2 and TNF-[alpha] on the glutathione (GSH) redox system in an human type II epithelial cell line (A549) in vitro. Cigarette smoke condensate, 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 oxidised GSH (GSSG), protein-GSH mixed disulfides (PrSSG), nor any glutathione efflux from the cells. By contrast, H2O2 (500[mu]M) after 5 minutes 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 1000 U/ml, produced a significant depletion of GSH in A549 cells after 4 and 24 hours exposure, with an associated elevation of GSSG. The activities of glutathione peroxidase, -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] occurs by different mechanisms.

Received 8 June 1994; accepted in final form 23 March 1995.
APS Manuscript Number L161-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 16 May 1995.