Redox Regulation of γ-Glutamyl Transpeptidase

Abstract

g-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, GGT plays important roles in glutathione homeostasis and mercapturic acid metabolism. The expression of GGT is increased as an adaptive response upon the exposure of oxidative stress. The underlying mechanism of this, however, is nebulous, as GGT 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 GGT 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.

Successful Interferon Therapy Reverses Enhanced Hepatic Progenitor Cell Activation in Patients with Chronic Hepatitis C

“…In chronic HCV infection, HPC activation can be induced by the inhibitory effects of IFN-gamma and tumor necrosis factoralpha, which are inflammatory cytokines overexpressed in HCV livers (Napoli and others 1996;Gochee and others 2003) during mature hepatocyte replication (Fausto 2004). GGT plays an important role in antioxidant defense, participating in the metabolism of glutathione (Zhang and Forman 2009), and it is upregulated following exposure to oxidative stress (Ravuri and others 2011). Oxidative stress inhibits the replication of mature hepatocytes, resulting in the activation of HPCs (Roskams and others 2003).…”

RETRACTED: <i>Gamma-Glutamyl Transferase Activity in Kids Born from Goats Fed Genetically Modified Soybean</i>

“…GGT is a membrane bound enzyme widely distributed in mammalian tissues which are involved in absorption and secretion [5]. High levels of GGT are constitutively expressed mainly in the liver and serum levels have significance in medicine as a diagnostic marker [6,7].…”

Human GGT2 Does Not Autocleave into a Functional Enzyme: A Cautionary Tale for Interpretation of Microarray Data on Redox Signaling

“…Before their death, the mice develop symptoms of severe redox stress, including cataracts and increased levels of DNA damage (8,42). In addition to its function in normal physiology, GGT1 is induced in some cells during redox stress via NFkB-and Nrf2-mediated pathways (55). It is induced in many tumors, contributing to their resistance to alkylating agents and other classes of chemotherapeutic drugs (15,16).…”