Evidence for the pro-oxidant effect of gamma-glutamyltranspeptidase-related enzyme.
It has been previously reported that the metabolism of reduced glutathione (GSH) by gamma-glutamyltranspeptidase ( GGT) in the presence of chelated metals leads to free radical generation and lipid peroxidation (LPO). The present study demonstrates for the first time that an established cell line expressing GGT-rel, a human GGT-related enzyme, metabolizes extracellular GSH to cysteinylglycine (CysGly) in a time-dependent manner when cells were incubated in a medium containing 2.5 mM GSH and 25 mM glycylglycine. Supplementation with 150-165 microM Fe(3+)-EDTA resulted in a reactive oxygen species (ROS) generation process. The resulting data showed a significantly higher level (7.6-fold) of ROS production in the GGT-rel positive cells in comparison with the GGT-rel negative control cells. CysGly and Cys, but not GSH, were responsible for the observed ROS production, as we confirmed by measuring the same process in the presence of Fe(3+)-EDTA and different thiols. A higher iron reduction and an increased LPO level determined by malondialdehyde HPLC measurement were also found in GGT-rel-overexpressing cells compared to GGT-rel negative cells. Our data clearly indicate that in the presence of iron, not only GGT, but also GGT-rel has a pro-oxidant function by generation of a reactive metabolite (CysGly) and must be taken into account as a potential physiopathological oxidation system.[1]References
- Evidence for the pro-oxidant effect of gamma-glutamyltranspeptidase-related enzyme. Enoiu, M., Aberkane, H., Salazar, J.F., Leroy, P., Groffen, J., Siest, G., Wellman, M. Free Radic. Biol. Med. (2000) [Pubmed]
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