Iron overload triggers redox-sensitive signals in human IMR-32 neuroblastoma cells

• Autores: Salvador, Gabriela Alejandra; Oteiza, Patricia Isabel
• Año de publicación: 2011
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Iron; Nfkb; Ap-1; Oxidative Stress; Neurotoxicity
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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-êB were investigated. Incubation with FAC (150ìM) 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-êB-DNA binding. This was associated with the upstream activation of the mitogen activated kinases ERK1/2, p38 and JNK and of IêBá 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.
Fil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Oteiza, Patricia Isabel. University Of California. Department Of Nutrition And Department Of Environmental Toxicology; Estados Unidos