Gamma-glutamyltranspeptidase-dependent glutathione catabolism results in activation of NF-kB.
gamma-glutamyltranspeptidase (GGT) is a key enzyme implicated in the homeostasis of intracellular reduced glutathione (GSH) and hence in the regulation of the cellular redox state. Besides, the extracellular cleavage of GSH by GGT leads to reactive oxygen species (ROS) production, depending on the generation and enhanced reactivity of cysteinylglycine (CysGly). Using a model cell line, the V79 GGT, which highly expresses a human GGT transgene, we examined whether the GGT induced oxidant stress could modulate intracellular transcription factors. For the first time, we show that GGT-dependent ROS production induces the NF-kB-binding and transactivation activities. This induction mimicked the one observed by H(2)O(2) and was inhibited by catalase, suggesting the involvement of H(2)O(2) in the NF-kB activation.
Accaoui
M J
MJ
Centre du Médicament EA 3117, Faculty of Pharmacy, Université Henry Poincaré Nancy I, 30 rue Lionnois, Nancy, 54000, France.
Enoiu
M
M
Mergny
M
M
Masson
C
C
Dominici
S
S
Wellman
M
M
Visvikis
A
A
D000818:Animals; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D004151:Dipeptides / Q000378:metabolism; D005347:Fibroblasts; D017930:Genes, Reporter / Q000235:genetics; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D019076:Transgenes / Q000235:genetics; D005723:gamma-Glutamyltransferase / Q000235:genetics / Q000378:metabolism*
D004151:Dipeptides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C028505:cysteinylglycine; D006861:Hydrogen Peroxide; D002374:Catalase; D005723:gamma-Glutamyltransferase; D005978:Glutathione