Oxygen-induced pulmonary injury in γ-glutamyl transpeptidase-deficient mice

Roberto Barrios, Zheng-Zheng Shi, Subbarao V. Kala, Amy L. Wiseman, Stephen E. Welty, Geeta Kala, Andrew A. Bahler, Ching Nan Ou, Michael W. Lieberman

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


We used mice with a targeted disruption in γ-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 ∼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 γ-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.

Original languageEnglish (US)
Pages (from-to)319-330
Number of pages12
Issue number5
StatePublished - 2001


  • Acute lung injury
  • Antioxidants
  • Glutathione
  • Hyperoxia
  • Oxidative stress
  • Respiratory distress syndrome

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology


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