Quiescence induced by iron challenge protects neuroblastoma cells from oxidative stress.
The brain uses massive amounts of oxygen, generating large quantities of reactive oxygen species (ROS). Because of its lipid composition, rich in unsaturated fatty acids, the brain is especially vulnerable to ROS. Furthermore, oxidative damage in the brain is often associated with iron, which has pro-oxidative properties. Iron-mediated oxidative damage in the brain is compounded by the fact that brain iron distribution is non-uniform, being particularly high in areas sensitive to neurodegeneration. This work was aimed to further our understanding of the cellular mechanisms by which SHSY5Y neuroblastoma cells adapt to, and survive increasing iron loads. Using an iron accumulation protocol that kills about 50% of the cell population, we found by cell sorting analysis that the SHSY5Y sub-population that survived the iron loading arrested in the G(0) phase of the cell cycle. These cells expressed neuronal markers, while their electrical properties remained largely unaltered. These results suggest that upon iron challenge, neuroblastoma cells respond by entering the G(0) phase, somehow rendering them resistant to oxidative stress. A similar physiological condition might be involved in neuronal survival in tissues known to accumulate iron with age, such as the hippocampus and the substantia nigra pars compacta.
Mura
Casilda V
CV
Department of Biology, Faculty of Sciences, University of Chile, Santiago, Chile.
Delgado
Ricardo
R
Aguirre
Pabla
P
Bacigalupo
Juan
J
Núñez
Marco T
MT
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*
C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D007501:Iron