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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / genetics
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Apoptosis / physiology*
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Cell Line
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Cell Survival / drug effects
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Cell Survival / physiology
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Cells, Cultured
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Cloning, Molecular
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Culture Media, Serum-Free
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Etoposide / pharmacology
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Fibroblasts / pathology
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Gene Deletion
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Heme Oxygenase (Decyclizing) / deficiency
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Heme Oxygenase (Decyclizing) / genetics*
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Heme Oxygenase (Decyclizing) / metabolism*
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Heme Oxygenase-1
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Humans
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Iron / metabolism*
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Membrane Proteins
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Mice
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Mice, Knockout
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Recombinant Proteins / metabolism
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Skin / cytology
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Skin / drug effects
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Skin / metabolism*
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Staurosporine / pharmacology
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Transfection
Substances
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Culture Media, Serum-Free
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Membrane Proteins
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Recombinant Proteins
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Etoposide
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Iron
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HMOX1 protein, human
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Heme Oxygenase (Decyclizing)
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Heme Oxygenase-1
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Hmox1 protein, mouse
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Staurosporine