Inhibition of phosphatidylserine synthesis in Jurkat T cells by hydrogen peroxide.
Incubation of Jurkat cells in the presence of H2O2 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 H2O2 induced inhibition of phosphatidylserine synthesis with an IC(50)=5 microM while both induction of tyrosine phosphorylation of proteins and Ca(2+) signals were obtained with an EC(50)=300 microM. The tyrosine kinase and Ca(2+) independent mechanism was confirmed by comparing the H2O2-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 p72syk, ZAP-70 and p56lck. While CD3-induced inhibition of phosphatidylserine synthesis necessitates protein tyrosine phosphorylation and Ca(2+) signals, H2O2 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.
Pelassy
C
C
INSERM U343, Hôpital de l'Archet, BP No. 79, 06202 Cedex 03, Nice, France.
Breittmayer
J P
JP
Aussel
C
C
D000975:Antioxidants / Q000494:pharmacology; D001692:Biological Transport; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D019169:Jurkat Cells; D010718:Phosphatidylserines / Q000096:biosynthesis*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D000975:Antioxidants; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D002083:Butylated Hydroxyanisole; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases; D002118:Calcium