Haem oxygenase-1 overexpression alters intracellular iron distribution

Lilibeth Lanceta, Chi Li, Augustine M. Choi, John W. Eaton

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Induction or ectopic overexpression of HO-1 (haem oxygenase 1) protects against a wide variety of disorders. These protective effects have been variably ascribed to generation of carbon monoxide (released during cleavage of the alpha-methene bridge of haem) and/or to production of the antioxidant bilirubin. We investigated HO-1-overexpressing A549 cells and find that, as expected, HO-1-overexpressing cells are resistant to killing by hydrogen peroxide. Surprisingly, these cells have approximately twice the normal amount of intracellular iron which usually tends to amplify oxidant killing. However, HO-1-overexpressing cells contain only ∼25% as much 'loose' (probably redox active) iron. Indeed, inhibition of ferritin synthesis [via siRNA (small interfering RNA) directed at the ferritin heavy chain] sensitizes the HO-1-overexpressing cells to peroxide killing. It appears that HO-1 overexpression leads to enhanced destruction of haem, consequent 2-3-fold induction of ferritin, and compensatory increases in transferrin receptor expression and haem synthesis. However, there is no functional haem deficiency because cellular oxygen consumption and catalase activity are similar in both cell types.We conclude that, at least in many cases, the cytoprotective effects of HO-1 induction or forced overexpression may derive from elevated expression of ferritin and consequent reduction of redox active 'loose' iron.

Original languageEnglish (US)
Pages (from-to)189-194
Number of pages6
JournalBiochemical Journal
Volume449
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Apoptosis
  • Ferritin
  • Haem oxygenase-1 (HO-1)
  • Lysosomes
  • Oxidant stress
  • Redox active iron

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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