Gamma-glutamyltranspeptidase-dependent glutathione catabolism results in activation of NF-kB

gamma-glutamyltranspeptidase (GGT) is a key enzyme implicated in the homeos tasis of intracellular reduced glutathione (GSH) and hence in the regulatio n of the cellular redox state. Besides, the extracellular cleavage of GSH b y GGT leads to reactive oxygen species (ROS) production, depending on the g eneration and enhanced reactivity of cysteinylglycine (CysGly). Using a mod el cell Line, the V79 GGT, which highly expresses a human GGT transgene, we examined whether the GGT induced oxidant stress could modulate intracellul ar transcription factors. For the first time, we show that GGT-dependent RO S production induces the NF-kB-binding and transactivation activities. This induction mimicked the one observed by H2O2 and was inhibited by catalase, suggesting the involvement of H2O2 in the NF-kB activation. (C) 2000 Acade mic Press.