Oxygen-induced pulmonary injury in γ-glutamyl transpeptidase-deficient mice Academic Article uri icon


MeSH Major

  • Acetylcysteine
  • Glutathione
  • Hyperoxia
  • Lung Injury
  • gamma-Glutamyltransferase


  • We used mice with a targeted disruption in g-glutamyl transpeptidase (GGT-deficient mice) to study the role of glutathione (GSH) in protection against oxygen-induced lung injury. These mice had reduced levels of lung GSH and restricted ability to synthesize GSH because of low levels of cysteine. When GGT-deficient mice were exposed to 80% oxygen, they developed diffuse pulmonary injury and died within eight days. Ten of 12 wild-type mice were alive after 18 days. Administration of N-acetylcysteine (NAC) to GGT-deficient mice corrected GSH values and prevented the development of severe pulmonary injury and death. Oxygen exposure induced an increase in lung GSH levels in both wild-type and GGT-deficient mice, but induced levels in the mutant mice were <50% of those in wild-type mice. Cysteine levels were approximately 50-fold lower than GSH levels the lungs of both wild-type and GGT-deficient mice. Levels of lung RNA coding for the heavy subunit of g-glutamyl cysteine synthetase rose three- to fourfold after oxygen exposure in both wild-type and GGT-deficient mice. In contrast, oxygen exposure failed to provoke increases in glutathione synthetase, glutathione peroxidase, glutaredoxin, or thioredoxin.

publication date

  • December 2001



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1007/s004080000071

PubMed ID

  • 11976899

Additional Document Info

start page

  • 319

end page

  • 30


  • 179


  • 5