alpha-Lipoic acid and N-acetyl cysteine prevent zinc deficiency-induced activation of NF-kappaB and AP-1 transcription factors in human neuroblastoma IMR-32 cells.
This work investigated the capacity of alpha-lipoic acid (LA) and N-acetyl-L-cysteine (NAC) to reduce zinc deficiency-induced oxidative stress, and prevent the activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), and the cross-talk between both activated cascades through beta-Transducin Repeat-containing Protein (beta-TrCP). IMR-32 cells were incubated in control media or media containing variable concentrations of zinc, without or with 0.5 mM LA or 1 mM NAC. Relative to control and zinc supplemented (15 microM Zn) groups, Hydrogen peroxide (H(2)O(2)) and total oxidant cell concentrations were higher, and total glutathione concentrations were lower in the zinc deficient groups (1.5 and 5 microM Zn). Both, LA and NAC, markedly reduced the increase in cell oxidants and the reduction in glutathione concentrations in the zinc deficient cells. Consistent with this, LA and NAC prevented zinc deficiency-induced activation of the early steps of NF- kappaB (IkappaBalpha phosphorylation) and AP-1 [c-Jun-N-terminal kinase (JNK) and p38 phophorylation] cascades, and the high NF-kappaB- and AP-1-DNA binding activities in total cell extracts. Thus, LA and NAC can reduce the oxidative stress associated with zinc deficiency and the subsequent triggering of NF-kappaB- and AP-1-activation in neuronal cells.
Mackenzie
Gerardo G
GG
Department of Biological Chemistry, IQUIFIB, UBA-CONICET, School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, C1113AAD, Argentina.
Zago
M Paola
MP
Erlejman
Alejandra G
AG
Aimo
Lucila
L
Keen
Carl L
CL
Oteiza
Patricia I
PI
D000111:Acetylcysteine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D008063:Thioctic Acid / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015032:Zinc / Q000172:deficiency* / Q000494:pharmacology
D016328:NF-kappa B; D016877:Oxidants; D018808:Transcription Factor AP-1; D008063:Thioctic Acid; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; D015032:Zinc; D000111:Acetylcysteine