Divergent modulation of iron regulatory proteins and ferritin biosynthesis by hypoxia/reoxygenation in neurons and glial cells

Carlo Irace, Antonella Scorziello, Carmen Maffettone, Giuseppe Pignataro, Carmela Matrone, Annagrazia Adornetto, Rita Santamaria, Lucio Annunziato, Alfredo Colonna

Research output: Contribution to journalArticlepeer-review

Abstract

Ferritin, the main iron storage protein, exerts a cytoprotective effect against the iron-catalyzed production of reactive oxygen species, but its role in brain injury caused by hypoxia/reoxygenation is unclear. Ferritin expression is regulated mainly at post-transcriptional level by iron regulatory proteins (IRP1 and IRP2) that bind specific RNA sequences (IREs) in the 5′ untranslated region of ferritin mRNA. Here, we show that hypoxia decreases IRP1 binding activity in glial cells and enhances it in cortical neurons. These effects were reversed by reoxygenation in both cell types. In glial cells there was an early increase of ferritin synthesis during hypoxia and reoxygenation. Conversely, in cortical neurons, ferritin synthesis increased during the late phase of reoxygenation. Steady-state analysis of ferritin mRNA levels suggested that ferritin synthesis is regulated mainly post-transcriptionally by IRPs in glioma cells, both transcriptionally and post-transcriptionally in type-1 astrocytes, and mainly at transcriptional level in an IRP-independent way in neurons. The different regulation of ferritin expression may account for the different vulnerability of neurons and glial cells to the injury elicited by oxygen and glucose deprivation (OGD)/reoxygenation. The greater vulnerability of cortical neurons to hypoxia-reoxygenation was strongly attenuated by the exogenous administration of ferritin during OGD/reoxygenation, suggesting the possible cytoprotective role exerted by this iron-segregating protein.

Original languageEnglish
Pages (from-to)1321-1331
Number of pages11
JournalJournal of Neurochemistry
Volume95
Issue number5
DOIs
Publication statusPublished - Dec 2005

Keywords

  • Ferritin
  • Hypoxia/reoxygenation
  • Iron metabolism
  • Iron regulatory proteins
  • Neuronal vulnerability
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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