Haem oxygenase-1 prevents cell death by regulating cellular iron

Christopher D. Ferris, Samie R. Jaffrey, Akira Sawa, Masaaki Takahashi, Stephen D. Brady, Roxanne K. Barrow, Steven A. Tysoe, Herman Wolosker, David E. Barañano, Sylvain Doré, Kenneth D. Poss, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

Abstract

Haem oxygenase-1 (HO1) is a heat-shock protein that is induced by stressful stimuli. Here we demonstrate a cytoprotective role for HO1: cell death produced by serum deprivation, staurosporine or etoposide is markedly accentuated in cells from mice with a targeted deletion of the HO1 gene, and greatly reduced in cells that overexpress HO1. Iron efflux from cells is augmented by HO1 transfection and reduced in HO1-deficient fibroblasts. Iron accumulation in HO1-deficient cells explains their death: iron chelators protect HO1-deficient fibroblasts from cell death. Thus, cytoprotection by HO1 is attributable to its augmentation of iron efflux, reflecting a role for HO1 in modulating intracellular iron levels and regulating cell viability.

Original languageEnglish (US)
Pages (from-to)152-157
Number of pages6
JournalNature cell biology
Volume1
Issue number3
DOIs
StatePublished - Jul 1999

ASJC Scopus subject areas

  • Cell Biology

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