QUINONES INCREASE GAMMA-GLUTAMYL-TRANSPEPTIDASE EXPRESSION BY MULTIPLE MECHANISMS IN RAT LUNG EPITHELIAL-CELLS

gamma-Glutamyl transpeptidase (GGT) plays an important role in glutath ione (GSH) metabolism. GGT expression is increased in oxidant-challeng ed cells; however, the signaling mechanisms involved are uncertain. Th e present study used 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), a redox cycling quinone that continuously produced H2O2 in rat lung epithelial L2 cells. It was found that DMNQ increased GGT mRNA content by increa sing transcription, as measured by nuclear run-on. This was accompanie d by increased GGT specific activity. Cycloheximide, a protein synthes is inhibitor, blocked neither the increased GGT mRNA content nor the i ncreased GGT transcription rate caused by DMNQ, suggesting that increa sed GGT transcription was a direct rather than secondary response. Pre vious data fi om this laboratory (R.-M. Liu, H. Hu, T. W. Robison, and H. J. Forman. Am. J. Respir. Cell Mel. Biol. 14: 186-191, 1996) showe d that; tert-butylhydroquinone (TBHQ) increased GGT mRNA content by in creasing its stability. TBHQ differs markedly from DMNQ in terms of it s conjugation with GSH and H2O2 generation. Together, the data suggest that quinones upregulate GGT through multiple mechanisms, increased t ranscription and posttranscriptional modulation, which are apparently mediated through generation of reactive oxygen species and GSH conjuga te formation, respectively.