Redox Regulation of γ-Glutamyl Transpeptidase

gamma-Glutamyl transpeptidase (GGT) catalyzes the transfer of the glutamyl moiety from glutathione, and glutathione S-conjugates to acceptors to form another amide or to water to produce free glutamate. Functionally, GIST plays important roles in glutathione homeostasis and mercapturic acid metabolism. The expression of GIST is increased as an adaptive response upon the exposure of oxidative stress. The underlying mechanism of this, however, is nebulous, as GIST gene structure is complex and its transcription is usually controlled by multiple promoters that generate several subtypes of GGT mRNAs. Studies reveal that signaling pathways such as Ras, ERK, p38MAPK, and PI3K are involved in the induction of GIST gene expression in response to oxidative stress. Thus, not surprisingly, induction of GGT mRNA subtypes and the involvement of multiple signaling pathways vary depending on cell type and stimuli.