Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5855511 | NeuroToxicology | 2011 | 8 Pages |
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.
Keywords
PAGEphosphorylated JNK4-(2-hydroxyethyl)-1-piperazineethanesulfonicDCDHFp-p38p-ERKc-Jun-N-terminal kinasephosphorylated p38PARPAP-1DTTDcfHEPESFACNF-κBPBSDMEMSDSJnkFBSDulbecco's modified Eagle MediumPhosphorylated ERKERK1/2MAPKsMitogen activated protein kinasesp-JnkElectrophoretic mobility shift assayIronFerric Ammonium CitrateEDTAethylenediamine tetraacetatepolyacrylamide gel electrophoresisOct-1Alzheimer's diseaseanalysis of varianceANOVAOxidative stressdithiothreitolsodium dodecyl sulfatefetal bovine serumNeurotoxicityEMSA یا electrophoretic mobility shift assay nuclear factor-κBPhosphate-buffered salineactivator protein-1propidium iodinepoly (ADP-ribose) polymeraseextracellular signal-regulated kinase
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Authors
Gabriela A. Salvador, Patricia I. Oteiza,