Editor-in-Chief İlkay Küçükgüzel Associate Editor Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Marmara Pharmaceutical Journal 2011 , Vol 15 , Issue 1
The pro-oxidant effect of platelet gamma-glutamyltransferase in the presence of iron(III)
Azize Şener1, Özge Çevik1, Derya Özsavcı1, Gülderen Yanıkkaya-Demirel2
1Marmara Üniversitesi, Eczacılık Fakültesi, Biyokimya Anabilim Dalı, İstanbul, Türkiye
2Yeditepe Üniversitesi, Tıbbi Mikrobiyoloji-İmmunoloji Anabilim Dalı, İstanbul, Türkiye
DOI : 10.12991/201115442 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. Keywords : platelet, gamma-glutamyl transferase, glutathione, oxidative stress, apoptosis, iron toxicity
Marmara University