Rm. Liu et al., QUINONES INCREASE GAMMA-GLUTAMYL-TRANSPEPTIDASE EXPRESSION BY MULTIPLE MECHANISMS IN RAT LUNG EPITHELIAL-CELLS, American journal of physiology. Lung cellular and molecular physiology, 18(3), 1998, pp. 330-336
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.