Erythrocytes as targets for gamma-glutamyltranspeptidase initiated pro-oxidant reaction.
Gamma-glutamyltranspeptidase (GGT) is a well known cell plasma membrane and serum circulating enzyme. In clinical chemistry, GGT is used as a marker of alcohol consumption and drug uptake. Serum GGT activity varies in hepatobiliary diseases and cancer. This enzyme is involved in glutathione (GSH) metabolism, which is generally associated with antioxidant properties. However, in recent years, findings from our group and from others showed that GGT-catalysed extracellular metabolism of GSH leads, in the presence of iron, to the generation of reactive oxygen species (ROS). It was demonstrated that those highly reactive species oxidise lipids, cell surface protein thiols or activate transcriptional factors such as Nuclear Factor kappaB (NFkappaB). The objective of the present work is to determine whether the red blood cells are targets for plasma GGT-initiated pro-oxidant reaction. The results obtained demonstrate that the GGT/GSH/iron system oxidises isolated erythrocyte membranes. A significant release of haemoglobin and a decrease of erythrocyte deformability are also observed. In addition, in vivo studies showed a relationship between plasma GGT activity and erythrocyte deformability in 20 studied subjects. In conclusion, GGT-mediated ROS production is able to oxidise erythrocytes and thus disturbs their functions.
Aberkane
Hayet
H
Thiols et Fonctions Cellulaires, Faculty of Pharmacy, University Henri Poincaré, Nancy 1, 30 rue Lionnois, 54000 Nancy, France.
Stoltz
Jean-François
JF
Galteau
Marie-Madeleine
MM
Wellman
Maria
M
D004907:Erythrocyte Deformability / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007501:Iron / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D016877:Oxidants / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism* / Q000494:pharmacology
D016877:Oxidants; D017382:Reactive Oxygen Species; D007501:Iron; D005723:gamma-Glutamyltransferase; D005978:Glutathione