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

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...

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Detalles Bibliográficos
Autores: Mackenzie, Gerardo G., Zago, María Paola, Erlejman, Alejandra Giselle, Aimo, Lucila, Keen, Carl L., Oteiza, Patricia Isabel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2006
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/36979
Acceso en línea:http://hdl.handle.net/11336/36979
Access Level:acceso abierto
Palabra clave:Ap-1
Lipoic Acid
N-Acetyl-Cysteine
Nf-Κb
Zinc
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario: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.