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

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 (150μM) resulted in a time (3-72h)-dependent increase in cellular iron content, and was associated with cell oxidant increase. FAC caused a time-dependent (3-48h) 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 72h incubation with FAC, cell viability was 40% lower than in controls. Iron overload caused apoptotic cell death. After 48-72h 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.

• Authors: Gabriela A Salvador, Patricia I Oteiza
• Journal: Neurotoxicology (Neurotoxicology) Vol. 32 Issue 1 Pg. 75-82 (Jan 2011) ISSN: 1872-9711 [Electronic] Netherlands
• PMID: 21130806 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Ferric Compounds
• Quaternary Ammonium Compounds
• ferric ammonium citrate

Topics

• Cell Line, Tumor
• Cell Survival (drug effects, physiology)
• Ferric Compounds (toxicity)
• Humans
• Iron Overload (chemically induced, metabolism, pathology)
• Neuroblastoma (metabolism, pathology)
• Oxidation-Reduction (drug effects)
• Quaternary Ammonium Compounds (toxicity)
• Signal Transduction (drug effects, physiology)