Iron overload triggers redox-sensitive signals in human IMR-32 neuroblastoma cells

Gabriela A. Salvador, Patricia I. Oteiza

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Excessive neuronal iron has been proposed to contribute to the pathology of several neurodegenerative diseases including Alzheimer's and Parkinson's diseases. This work characterized human neuroblastoma IMR-32 cells exposure to ferric ammonium citrate (FAC) as a model of neuronal iron overload and neurodegeneration. The consequences of FAC treatment on neuronal oxidative stress and on the modulation of the oxidant-sensitive transcription factors AP-1 and NF-κB were investigated. Incubation with FAC (150 μM) resulted in a time (3-72. h)-dependent increase in cellular iron content, and was associated with cell oxidant increase. FAC caused a time-dependent (3-48. h) increase in nuclear AP-1- and NF-κB-DNA binding. This was associated with the upstream activation of the mitogen activated kinases ERK1/2, p38 and JNK and of IκBα phosphorylation and degradation. After 72. h incubation with FAC, cell viability was 40% lower than in controls. Iron overload caused apoptotic cell death. After 48-72. h of incubation with FAC, caspase 3 activity was increased, and chromatin condensation and nuclear fragmentation were observed. In summary, the exposure of IMR-32 cells to FAC is associated with increased oxidant cell levels, activation of redox-sensitive signals, and apoptosis.

Original languageEnglish (US)
Pages (from-to)75-82
Number of pages8
JournalNeuroToxicology
Volume32
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Iron Overload
Neuroblastoma
Oxidation-Reduction
Iron
Oxidants
Transcription Factor AP-1
Chemical activation
MAP Kinase Kinase 4
Neurodegenerative diseases
B-Form DNA
Phosphorylation
Oxidative stress
Mitogen-Activated Protein Kinase 3
Pathology
Cell death
ferric ammonium citrate
Mitogens
Caspase 3
Neurodegenerative Diseases
Chromatin

Keywords

  • AP-1
  • Iron
  • Neurotoxicity
  • NF-κB
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Iron overload triggers redox-sensitive signals in human IMR-32 neuroblastoma cells. / Salvador, Gabriela A.; Oteiza, Patricia I.

In: NeuroToxicology, Vol. 32, No. 1, 01.2011, p. 75-82.

Research output: Contribution to journalArticle

Salvador, Gabriela A. ; Oteiza, Patricia I. / Iron overload triggers redox-sensitive signals in human IMR-32 neuroblastoma cells. In: NeuroToxicology. 2011 ; Vol. 32, No. 1. pp. 75-82.
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