Inhibition of phosphatidylserine synthesis in Jurkat T cells by hydrogen peroxide

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Incubation of Jurkat cells in the presence of H 2O 2 either directly added to the culture medium or generated with glucose oxidase, menadione or the couple xanthine/xanthine oxidase induced a marked decrease of phosphatidylserine synthesis in the absence of changes in the synthesis of phosphatidylcholine and phosphatidylethanolamine. Concentration dependent response curves indicated that H 2O 2 induced inhibition of phosphatidylserine synthesis with an IC 50=5 μM while both induction of tyrosine phosphorylation of proteins and Ca 2+ signals were obtained with an EC 50=300 μM. The tyrosine kinase and Ca 2+ independent mechanism was confirmed by comparing the H 2O 2-induced and the CD3-induced inhibition of phosphatidylserine synthesis using several Jurkat clones differing in the expression of cell surface receptors such as CD3/TCR and CD45 and protein tyrosine kinase such as p72 syk, ZAP-70 and p56 lck. While CD3-induced inhibition of phosphatidylserine synthesis necessitates protein tyrosine phosphorylation and Ca 2+ signals, H 2O 2 provoked its effect in all the clones studied independently of the presence or absence of the proteins previously shown to be key elements in T cell signal transduction. Conversely, the antioxidant molecule, butylated hydroxanisole, generates an increased PtdSer synthesis, suggesting that the synthesis of this phospholipid is regulated by the redox status of the cells.