Zinc deficiency-associated increase in oxidant levels affects the translocation of NF-kB and NFAT to the Nuclei by affecting tubulin polymerization

MACKENZIE G.G.; ERLEJMAN A.G.; OTEIZA P.I.

Santa Barbara, California, EEUU.

Congreso; Oxidants and antioxidants in biology. Annual meeting of the OXYGEN CLUB OF CALIFORNIA; 2006

OXYGEN CLUB OF CALIFORNIA

The role of oxidants and tubulin depolymerization on NF-kB and NFAT nuclear translocation associated with zinc deficiency were investigated in human neuroblastoma IMR-32 cells. 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 1 mM N-acetyl-L-cysteine (NAC) for 24 h. Total oxidant cell concentrations were higher and total glutathione concentrations were lower in the low zinc groups (1.5 and 5 Zn) compared to control and 15 Zn groups. LA or NAC prevented the increase in total oxidants levels, and restored glutathione concentration in the low zinc cells. Zinc deficiency induced NF-kB and NFAT activation as measured by EMSA in total cell extracts. However, NF-kB and NFAT accumulated in the cytosol. In the zinc deficient cells, a low rate of in vitro tubulin polymerization and of polymerized tubulin content was observed compared to the other groups, while the simultaneous incubation of zinc deficient cells with LA or NAC partially restored the nuclear translocation of the active NF- kB. In summary, a decrease in cellular zinc affects select transcription factors (NF-kB and NFAT) partially through an increase in cellular oxidants. Supported by grants from the NIH (HD 01743) and the University of California, Davis.