Hyperoxia enhances the expression of -glutamyl transpeptidase and
increases protein s-glutathiolation in rat lung.
Knickelbein, Roy G., David H. Ingbar, Tamas Seres, Kris Snow, Richard
B. Johnston, Jr, Olutoyin Fayemi, Francine Gumkowski, James D.
Jamieson, and Joseph B. Warshaw.
Departments of Pediatrics and Cell Biology, Yale University School
of Medicine, New Haven, CT 06520 and Department of Medicine,
University of Minnesota, Minneapolis, MN 55455
APStracts 2:0174L, 1995.
By participating in glutathione (GSH) synthesis, -glutamyl
transpeptidase (GGT) influences the GSH redox cycle which is a major
contributor in protecting against reactive oxygen metabolites. This
study determined the effect of prolonged exposure of neonatal rats to
>98% oxygen on expression of GGT and on GSH metabolism. Lungs of
neonatal rats chronically exposed to hyperoxia had increased
expression of GGT mRNA resulting in significantly higher GGT protein
levels and enzyme activity than in lungs of animals raised in room
air. Hyperoxia also upregulated glucose 6-phosphate dehydrogenase but
sodium-potassium-ATPase activity was not changed. GGT mRNA, protein
level and enzyme activity returned to control levels after recovery
in room air for 3 days. Levels of GSH, glutathione disulfide, and
protein-bound GSH (S-glutathiolated protein) rose with hyperoxia and
fell during recovery. S-glutathiolation is likely a mechanism for
protection and a regulatory modification of protein sulfhydryl
groups. Hyperoxia-induced upregulation of GGT and the concomitant
increase in protein S-glutathiolation appear to be additional
components fundamental in protecting the lung against oxidative
injury.
Received 3 May 1995; accepted in final form 18 August 1995.
APS Manuscript Number L132-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95