HYPEROXIA ENHANCES EXPRESSION OF GAMMA-GLUTAMYL-TRANSPEPTIDASE AND INCREASES PROTEIN S-GLUTATHIOLATION IN RAT LUNG

By participating in glutathione (GSH) synthesis, gamma-glutamyl transp eptidase (GGT) influences the GSH redox cycle, which is a major contri butor in protecting against reactive oxygen metabolites. This study de termined the effect of prolonged exposure of neonatal rats to >98% oxy gen 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 acti vity than in lungs of animals raised in room air. Hyperoxia also upreg ulated glucose-6-phosphate dehydrogenase, but Na-K-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 l ikely a mechanism for protection and a regulatory modification of prot ein sulfhydryl groups. Hyperoxia-induced upregulation of GGT and the c oncomitant increase in protein S-glutathiolation appear to be addition al components fundamental in protecting the lung against oxidative inj ury.