Quinones increase gamma-glutamyl transpeptidase expression by multiple mechanisms in rat lung epithelial cells

The American Journal of Physiology
R M LiuH J Forman

Abstract

gamma-Glutamyl transpeptidase (GGT) plays an important role in glutathione (GSH) metabolism. GGT expression is increased in oxidant-challenged cells; however, the signaling mechanisms involved are uncertain. The 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 increasing transcription, as measured by nuclear run-on. This was accompanied by increased GGT specific activity. Cycloheximide, a protein synthesis inhibitor, blocked neither the increased GGT mRNA content nor the increased GGT transcription rate caused by DMNQ, suggesting that increased GGT transcription was a direct rather than secondary response. Previous data from this laboratory (R.-M. Liu, H. Hu, T. W. Robinson, and H. J. Forman. Am. J. Respir. Cell Mol. Biol. 14: 186-191, 1996) showed that tert-butylhydroquinone (TBHQ) increased GGT mRNA content by increasing its stability. TBHQ differs markedly from DMNQ in terms of its conjugation with GSH and H2O2 generation. Together, the data suggest that quinones upregulate GGT through multiple mechanisms, increased transcription and posttranscriptional modulation, which are...Continue Reading

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Citations

Sep 10, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Rui-Ming LiuMargaret M Tarpey
Sep 16, 2005·American Journal of Physiology. Cell Physiology·André M CantinJohn W Hanrahan
Dec 18, 2002·Annals of the New York Academy of Sciences·Dale A Dickinson, Henry Jay Forman
Oct 21, 2009·The Journal of Physiology·Valerie P WrightThomas L Clanton
Aug 1, 2001·Current Protocols in Toxicology·R M LiuH J Forman
Dec 7, 2002·American Journal of Respiratory and Critical Care Medicine·Annie PardoMoisés Selman

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