The pro-oxidant effect of platelet gamma-glutamyltransferase in the presence of iron(III)

Gamma-glutamyltransferase (GGT), a plasma membran enzyme, plays important role in the reduced glutathione (GSH) metabolism. GGT activity during the catabolism of GSH originates the thiol dipeptide cysteinylglycine, whose-SH group is provided in particular with a much stronger iron-reducing ability. Recent research indicates that increased serum GGT activity could be used as a marker for increased oxidative stress in human. GGT activity is also found in platelets. Redox reactions can modify platelet functions. However, the role of platelet-GGT activity on its redox enviroment is unknown. The objective of the present work is to determine whether the platelet-bound GGT activity initiates oxidative modifications and apoptotic stimuli in presence of iron(III). In our study, lipid peroxidation, protein oxidation, GSH, phosphatidylserine (PS) and caspase-3 levels of platelets were investigated after inhibiting platelet GGT activity with inhibitors and/or stimulating platelet GGT activity with its substrates in the presence of iron(III). The resulting data showed significantly higher levels of lipid peroxidation and protein oxidation in the GGT activity-stimulated platelets in comparison with the GGT activity inhibited platelets in the presence of iron(III). GSH contents of the GGT activity-stimulated platelets were significantly reduced. No significant difference was observed caspase-3 activities of platelets. However, PS externalization in GGT activity stimulated platelets were increased compared to the GGT activityinhibited platelets in the early stage apoptosis/activation. Platelet-GGT/GSH/iron(III) system can induce oxidative modifications and PS externalization on human platelets. Thus, platelet bound-GGT may contribute to the increase of reactive oxygen species (ROS) in its enviroment and promote cardiovascular diseases.