Haem oxygenase-1 prevents cell death by regulating cellular iron

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 pro duced by serum deprivation, staurosporine or etoposide is markedly accentua ted in cells from mice with a targeted deletion of the HO1 gene, and greatl y reduced in cells that overexpress HO1. Iron efflux from cells is augmente d by HO1 transfection and reduced in HO1-deficient fibroblasts, Iron accumu lation in HO1-deficient cells explains their death: iron chelators protect HO1-deficient fibroblasts from cell death. Thus, cytoprotection by HO1 is a ttributable to its augmentation of iron efflux, reflecting a role for HO1 i n modulating intracellular iron levels and regulating cell viability.