Effects of anti-oxidants on ornithine decarboxylase in mitogenically-activated T lymphocytes.
Reactive oxygen species formation is an early event following lymphocyte activation and may trigger other biochemical processes. Anti-oxidants (desferrioxamine (DES), nordihydroguaiaretic acid (NDGA) and potassium ferricyanide) inhibit human and murine T cell proliferation in vitro. Since an increase in ornithine decarboxylase (ODC) activity is an essential concomitant of T lymphocyte proliferation, we have examined in vitro the effects of anti-oxidants on this activity increase. ODC activity in mouse lymph node T cells increased steadily from 6-24 h after addition of concanavalin A. The combination of phorbol myristate acetate (PMA) and ionomycin also stimulated ODC activity in these cells. The anti-oxidants DES, NDGA and ferricyanide strongly inhibited the increase in ODC activity seen in response to either concanavalin A or PMA/ionomycin. Dose-response curves for the inhibitory effects of the anti-oxidants on DNA synthesis and ODC activity at 48 h after mitogen addition were very similar. Addition of putrescine or spermidine (10-100 microM) could not overcome the block in DNA synthesis induced by DES. Although the anti-oxidants inhibited the ODC activity increase in mitogen-stimulated T cells, they did not decrease mRNA levels for the enzyme. These results suggest that intracellular formation of reactive oxygen species is involved in the induction of ODC activity by a mechanism exerted at a posttranscriptional stage. The anti-oxidants can be employed as tools to elucidate contingent relationships between some intracellular events that follow T cell activation.
Hunt
N H
NH
Department of Pathology, University of Sydney, Australia.
Fragonas
J C
JC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D005292:Ferricyanides / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009955:Ornithine Decarboxylase / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000975:Antioxidants; D005292:Ferricyanides; D012333:RNA, Messenger; D003208:Concanavalin A; D015759:Ionomycin; D009637:Masoprocol; D009955:Ornithine Decarboxylase; D003676:Deferoxamine; D013755:Tetradecanoylphorbol Acetate