Iron uptake in quiescent and inflammation-activated astrocytes: A potentially neuroprotective control of iron burden

Ilaria Pelizzoni, Daniele Zacchetti, Alessandro Campanella, Fabio Grohovaz, Franca Codazzi

Research output: Contribution to journalArticlepeer-review

Abstract

Astrocytes play a crucial role in proper iron handling within the central nervous system. This competence can be fundamental, particularly during neuroinflammation, and neurodegenerative processes, where an increase in iron content can favor oxidative stress, thereby worsening disease progression. Under these pathological conditions, astrocytes undergo a process of activation that confers them either a beneficial or a detrimental role on neuronal survival. Our work investigates the mechanisms of iron entry in cultures of quiescent and activated hippocampal astrocytes. Our data confirm that the main source of iron is the non-transferrin-bound iron (NTBI) and show the involvement of two different routes for its entry: the resident transient receptor potential (TRP) channels in quiescent astrocytes and the de novo expressed divalent metal transporter 1 (DMT1) in activated astrocytes, which accounts for a potentiation of iron entry. Overall, our data suggest that at rest, but even more after activation, astrocytes have the potential to buffer the excess of iron, thereby protecting neurons from iron overload. These findings further extend our understanding of the protective role of astrocytes under the conditions of iron-mediated oxidative stress observed in several neurodegenerative conditions. Non-transferrin-bound iron (NTBI) is the main source of iron for astrocytes. TRPC channels represent an entry pathway for Fe2+ in resting astrocytes. Activation process increases the competence of astrocytes to uptake iron. DMT1 expression accounts for potentiation of iron ingress in activated astrocytes.

Original languageEnglish
Pages (from-to)1326-1333
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1832
Issue number8
DOIs
Publication statusPublished - Aug 2013

Keywords

  • Activation process
  • Astrocytes
  • DMT1
  • Neuroinflammation
  • Non-transferrin-bound iron uptake
  • TRP channels

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

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