Iron homeostasis in neuronal cells: a role for IREG1

Miguel Arredondo,Natalia Mena,Marco T Núñez,Victoria Tapia,Pabla Aguirre

doi:10.1186/1471-2202-6-3

Miguel Arredondo, Natalia Mena + Show 3 more

Open Access

https://doi.org/10.1186/1471-2202-6-3

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Abstract

BackgroundIron 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.ResultsWe 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.ConclusionsNeuronal 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.

Highlights

Iron is necessary for neuronal function but in excess generates neurodegeneration
In this study we examined iron homeostasis in SH-SY5Y neuroblastoma cells and hippocampal neurons
Iron accumulation and cell death Iron accumulation was determined in SH-SY5Y cells grown to confluence and cultured for two days in media containing from 1.5 to 80 μM iron (Figure 1A)

Summary

Introduction

Iron is necessary for neuronal function but in excess generates neurodegeneration. Most of the components of the iron homeostasis machinery have been described in neurons, little is known about the particulars of their iron homeostasis. Brain antioxidant defenses function properly during most of human life, a number of neurodegenerative processes which involve redox-active iron accumulation become evident with age [3,4,5]. The crucial components of the iron homeostasis machinery have been identified. Current efforts should be directed to the understanding of the mechanisms that regulate cellular iron levels and antioxidant defenses. This is of primary importance for the development of strategies to ameliorate iron accumulation and oxidative damage in neurons

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