Increasing expression of H- or L-ferritin protects cortical astrocytes from hemin toxicity

Free Radic Res. 2009 Jun;43(6):613-21. doi: 10.1080/10715760902942808.

Abstract

Iron toxicity may contribute to oxidative injury in cells surrounding an intracerebral haematoma. Cells detoxify iron by sequestering it in ferritin, a 24-mer heteropolymer constructed of H and L subunits. The relative antioxidant efficacy of H- and L-ferritin has not been defined and was tested in this study using an established model of hemin toxicity. Consistent with prior observations, cultures treated with 30 microM hemin sustained loss of approximately half of the cells by 6 h, as measured by LDH and MTT assays, and a 14-fold increase in protein carbonyls. Increasing expression of either ferritin by adenoviral gene transfer prior to hemin treatment had a similar protective effect. Quenching of calcein fluorescence, a marker of the labile iron pool, in hemin-treated cultures was also equally reduced by either subunit. These results suggest that over-expression of either H- or L-ferritin protects astrocytes from hemin and may be beneficial after CNS haemorrhage.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoferritins / genetics
  • Apoferritins / metabolism*
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Blotting, Western
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Gene Transfer Techniques
  • Hemin / toxicity*
  • Mice

Substances

  • Hemin
  • Apoferritins