Astrocytes acquire resistance to iron-dependent oxidative stress upon proinflammatory activation

Romina Macco, Ilaria Pelizzoni, Alessandra Consonni, Ilaria Vitali, Giacomo Giacalone, Filippo Martinelli Boneschi, Franca Codazzi, Fabio Grohovaz, Daniele Zacchetti

Research output: Contribution to journalArticle

Abstract

Background: Astrocytes respond to local insults within the brain and the spinal cord with important changes in their phenotype. This process, overall known as "activation", is observed upon proinflammatory stimulation and leads astrocytes to acquire either a detrimental phenotype, thereby contributing to the neurodegenerative process, or a protective phenotype, thus supporting neuronal survival. Within the mechanisms responsible for inflammatory neurodegeneration, oxidative stress plays a major role and has recently been recognized to be heavily influenced by changes in cytosolic iron levels. In this work, we investigated how activation affects the competence of astrocytes to handle iron overload and the ensuing oxidative stress.Methods: Cultures of pure cortical astrocytes were preincubated with proinflammatory cytokines (interleukin-1β and tumor necrosis factor α) or conditioned medium from lipopolysaccharide-activated microglia to promote activation and then exposed to a protocol of iron overload.Results: We demonstrate that activated astrocytes display an efficient protection against iron-mediated oxidative stress and cell death. Based on this evidence, we performed a comprehensive biochemical and molecular analysis, including a transcriptomic approach, to identify the molecular basis of this resistance.Conclusions: We propose the protective phenotype acquired after activation not to involve the most common astrocytic antioxidant pathway, based on the Nrf2 transcription factor, but to result from a complex change in the expression and activity of several genes involved in the control of cellular redox state.

Original languageEnglish
Article number130
JournalJournal of Neuroinflammation
Volume10
DOIs
Publication statusPublished - Oct 28 2013

    Fingerprint

Keywords

  • Astrocyte activation
  • Cytokines
  • Iron
  • Microglia
  • Nrf2
  • Oxidative stress

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology
  • Immunology
  • Neuroscience(all)

Cite this