Iron homeostasis in neuronal cells: a role for IREG1.
BACKGROUND
Iron is necessary for neuronal function but in excess generates neurodegeneration. Although most of the components of the iron homeostasis machinery have been described in neurons, little is known about the particulars of their iron homeostasis. In this work we characterized the response of SH-SY5Y neuroblastoma cells and hippocampal neurons to a model of progressive iron accumulation.


RESULTS
We found that iron accumulation killed a large proportion of cells, but a sub-population became resistant to iron. The surviving cells evoked an adaptative response consisting of increased synthesis of the iron-storage protein ferritin and the iron export transporter IREG1, and decreased synthesis of the iron import transporter DMT1. Increased expression of IREG1 was further substantiated by immunocytochemistry and iron efflux experiments. IREG1 expression directly correlated with iron content in SH-SY5Y and hippocampal cells. Similarly, a high correlation was found between IREG1 expression and the rate of iron efflux from SH-SY5Y cells.


CONCLUSIONS
Neuronal survival of iron accumulation associates with increased expression of the efflux transporter IREG1. Thus, the capacity of neurons to express IREG1 may be one of the clues to iron accumulation survival.
Aguirre
Pabla
P
Department of Biology, Faculty of Sciences, University of Chile, Santiago, Chile. pabla_aguirre@biotecnologia.every1.net
Mena
Natalia
N
Tapia
Victoria
V
Arredondo
Miguel
M
Núñez
Marco T
MT
D000595:Amino Acid Sequence; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D000098742:Ferroportin
D027682:Cation Transport Proteins; D000098742:Ferroportin; D007501:Iron