A decrease in neuronal zinc triggers the oxidant-mediated activation of NF-kB and AP-1 in neuroblastoma cells

MACKENZIE, G.G.; ZAGO, M.P; ERLEJMAN, A.G; AIMO ,L.; CLEGG, M.S.; OTEIZA, P.I.

Ciudad de Buenos Aires, Argentina

Congreso; XII Biennial Meeting of the International Society for Free Radical Research; 2004

Society for Free Radical Research International

The role of oxidant on Nf-kB and Ap-1 activation associated with a decreased in intracellular zinc levels was investigated. IMR-32 cells were incubated in control media or chelated media containing 1.5, 5 or 15 mM zinc, without or with 0.5 mM alpha lipoic acid (LA) or 1mM N-acetyl-cystein (NAC) for 24h. H2O2 and total oxidant cell concentrations were higher and total glutathione concentrations were lower in the low zinc groups (1.5 and 5 zinc) compared to control and 15 zinc groups. LA or NAC prevent the increase in H2O2 and total oxidant levels, and restored glutathione concentration in the low zinc cells.  Zinc deficiency induced the activation of early step of NF-kB (IkB phosphorylation) and AP-1 (JNK and p38 phosphorylation) cascades and a high NF-kB and AP-1-DNA binding activity in the total cell extracts. LA and NAC prevent IkB, JNK and p38 phosphorylation, and Inhibited NF-kB and AP-1-DNA binding activity. Results demonstrated that alterations in the cell concentrations of oxidant and/or thiols, associated with a decrease in intracellular zinc, trigger NF-kB and AP-1activation in neuronal cells.