Evidence for the pro-oxidant effect of γ-glutamyltranspeptidase–related enzyme

It has been previously reported that the metabolism of reduced glutathione (GSH) by γ-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 express...

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Bibliographic Details
Published in:Free radical biology & medicine 2000-11, Vol.29 (9), p.825-833
Main Authors: Enoiu, Milica, Aberkane, Hayet, Salazar, Jean-Frédéric, Leroy, Pierre, Groffen, John, Siest, Gérard, Wellman, Maria
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Cysteine - metabolism
Cysteinylglycine
Dipeptides - metabolism
Free radicals
Free Radicals - metabolism
gamma-Glutamyltransferase - genetics
gamma-Glutamyltransferase - metabolism
Gamma-glutamyltransferase–related enzyme
Glutathione
Glutathione - metabolism
Glycylglycine - metabolism
Humans
Lipid Peroxidation
Mice
Oxidation-Reduction
Reactive Oxygen Species - metabolism
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Transfection
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Summary:It has been previously reported that the metabolism of reduced glutathione (GSH) by γ-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 μM 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.
ISSN:0891-5849
1873-4596
DOI:10.1016/S0891-5849(00)00370-1