Journal
NEUROTOXICOLOGY
Volume 32, Issue 1, Pages 75-82Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.neuro.2010.11.006
Keywords
Oxidative stress; Iron; Neurotoxicity; AP-1; NF-kappa B
Categories
Funding
- Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCYT)
- Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET, Argentina)
- University of California (Davis)
Ask authors/readers for more resources
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-kappa B were investigated. Incubation with FAC (150 mu M) 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-kappa B-DNA binding. This was associated with the upstream activation of the mitogen activated kinases ERK1/2, p38 and JNK and of I kappa B alpha 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. (C) 2010 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available