Author(s): Salvador GA, Oteiza PI
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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. Copyright © 2010 Elsevier Inc. All rights reserved.
This article was published in Neurotoxicology
and referenced in Journal of Environmental Analytical Chemistry