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 language | English (US) |
|---|---|
| Pages (from-to) | 75-82 |
| Number of pages | 8 |
| Journal | NeuroToxicology |
| Volume | 32 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2011 |
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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 journal › Article
}
TY - JOUR
T1 - Iron overload triggers redox-sensitive signals in human IMR-32 neuroblastoma cells
AU - Salvador, Gabriela A.
AU - Oteiza, Patricia I.
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
KW - AP-1
KW - Iron
KW - Neurotoxicity
KW - NF-κB
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=78951471098&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78951471098&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2010.11.006
DO - 10.1016/j.neuro.2010.11.006
M3 - Article
C2 - 21130806
AN - SCOPUS:78951471098
VL - 32
SP - 75
EP - 82
JO - NeuroToxicology
JF - NeuroToxicology
SN - 0161-813X
IS - 1
ER -