EXPRESSION AND REGULATION OF GAMMA-GLUTAMYL TRANSPEPTIDASE-RELATED ENZYME IN TRACHEAL CELLS

Glutathione plays an essential role in protecting the pulmonary system from toxic insults. gamma-Glutamyl transpeptidase-related enzyme (GGT -rel) is a novel protein capable of cleaving the gamma-glutamyl peptid e bond of glutathione and of converting leukotriene C-4 to leukotriene D-4. A rat homologue of GGT-rel was identified and was found to be hi ghly expressed in cultures of differentiating rat tracheal epithelial (RTE) cells. The 2.6-kb cDNA predicts a 572-amino acid protein with 79 % identity to human GGT-rel. GGT-rel was weakly expressed in normal tr achea but was strongly induced by epidermal growth factor in cultures of RTE cells. GGT-rel was also highly expressed in lung tumors induced by inhalation of isobutyl nitrite. These results demonstrate that GCT -rel 1) is expressed in normal tracheal cells, 2) can be induced by ep idermal growth factor, and 3) is elevated after chemical exposure. The induction of high levels of GGT-rel may play an important role in pro tecting the lung from oxidative stress or other toxic insults.