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.
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Acknowledgements
We thank R. Seaforth for providing [55Fe]haemin, D. C. Dodson for secretarial assistance, and S. Tonegawa for initial supplies of HO1−/− mice. This work was supported by USPHS grant MH-18501 and Research Scientist Award DA-00074 to S.H.S., and a National Research Service Award (DA-05900) to D.E.B. C.D.F. has a Howard Hughes Fellowship for Physicians and H.W. is a Pew Fellow.
Correspondence and requests for materials should be addressed to S.H.S. or C.D.F.
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Ferris, C., Jaffrey, S., Sawa, A. et al. Haem oxygenase-1 prevents cell death by regulating cellular iron. Nat Cell Biol 1, 152–157 (1999). https://doi.org/10.1038/11072
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DOI: https://doi.org/10.1038/11072
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