Iron overload triggers redox-sensitive signals in human IMR-32 neuroblastoma cells.
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.
Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional del Sur, CC857, Camino La Carrindanga Km 7, B8000FWB Bahía Blanca, Buenos Aires, Argentina. salvador@criba.edu.ar
Gabriela A
GA
Salvador
Patricia I
PI
Oteiza
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D005290:Ferric Compounds / Q000633:toxicity*; D006801:Humans; D019190:Iron Overload / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D005290:Ferric Compounds; D000644:Quaternary Ammonium Compounds; C013531:ferric ammonium citrate