Expression of gamma-glutamyl transpeptidase mRNA after depletion of glutathione in rat liver

Gamma-glutamyl transpeptidase (γ-GT) is the enzyme in the γ-glutamyl cycle which mediates the first step of glutathione degradation. Recently, it has been reported that diethyl maleate, a glutathione-depleting agent, enhanced hepatic γ-GT activity. In this study, we examined how γ-GT mRNA was expressed after the depletion of glutathione by using the RT-PCR method and in situ hybridization technique with digoxigenin-labeled oligonucleotide probe. We could detect hepatic γ-GT mRNA in the epithelial cell of bile duct and the cytoplasm of hepatocytes in the periportal area, even in control rats. Furthermore, we found that the expression of γ-GT mRNA was expanded to hepatocytes of a whole lobule 12 hr after depletion of glutathione by diethyl maleate, followed by the return to the pretreatment condition under which γ-GT mRNA appears to be controlled in correlation with hepatic glutathione levels. These results suggest that the depletion of glutathione may induce hepatic γ-GT activity through an increased synthesis of its mRNA.