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 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.
Ferris, CD; Jaffrey, SR; Sawa, A; Takahashi, M; Brady, SD; Barrow, RK; Tysoe, SA; Wolosker, H; Barañano, DE; Doré, S; Poss, KD; Snyder, SH
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