α-Lipoic acid and N-acetyl cysteine prevent zinc deficiency-induced activation of NF-κB and AP-1 transcription factors in human neuroblastoma IMR-32 cells

Gerardo Mackenzie, M. Paola Zago, Alejandra G. Erlejman, Lucila Aimo, Carl L Keen, Patricia I. Oteiza

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

This work investigated the capacity of α-lipoic acid (LA) and N-acetyl-l-cysteine (NAC) to reduce zinc deficiency-induced oxidative stress, and prevent the activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), and the cross-talk between both activated cascades through β-Transducin Repeat-containing Protein (β-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 μM Zn) groups, Hydrogen peroxide (H2O2) and total oxidant cell concentrations were higher, and total glutathione concentrations were lower in the zinc deficient groups (1.5 and 5 μM 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- κB (IκBα phosphorylation) and AP-1 [c-Jun-N-terminal kinase (JNK) and p38 phophorylation] cascades, and the high NF-κB- 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-κB- and AP-1-activation in neuronal cells.

Original languageEnglish (US)
Pages (from-to)75-84
Number of pages10
JournalFree Radical Research
Volume40
Issue number1
DOIs
StatePublished - Jan 2006

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Acetylcysteine
Thioctic Acid
Transcription Factor AP-1
Neuroblastoma
Cysteine
Zinc
Transcription Factors
Chemical activation
Oxidative stress
Oxidants
Glutathione
Oxidative Stress
Transducin
Phosphorylation
JNK Mitogen-Activated Protein Kinases
Cell Extracts
Hydrogen Peroxide
DNA

Keywords

  • AP-1
  • Lipoic acid
  • N-acetyl-cysteine
  • NF-κB
  • Zinc

ASJC Scopus subject areas

  • Biochemistry

Cite this

α-Lipoic acid and N-acetyl cysteine prevent zinc deficiency-induced activation of NF-κB and AP-1 transcription factors in human neuroblastoma IMR-32 cells. / Mackenzie, Gerardo; Zago, M. Paola; Erlejman, Alejandra G.; Aimo, Lucila; Keen, Carl L; Oteiza, Patricia I.

In: Free Radical Research, Vol. 40, No. 1, 01.2006, p. 75-84.

Research output: Contribution to journalArticle

Mackenzie, Gerardo ; Zago, M. Paola ; Erlejman, Alejandra G. ; Aimo, Lucila ; Keen, Carl L ; Oteiza, Patricia I. / α-Lipoic acid and N-acetyl cysteine prevent zinc deficiency-induced activation of NF-κB and AP-1 transcription factors in human neuroblastoma IMR-32 cells. In: Free Radical Research. 2006 ; Vol. 40, No. 1. pp. 75-84.
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