Haem oxygenase-1 prevents cell death by regulating cellular iron
Haem oxygenase-1 prevents cell death by regulating cellular iron
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DOI：
10.1038/11072
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发表时间：
1999-07-01
影响因子：
21.3
通讯作者：
Snyder, SH
中科院分区：
文献类型：
--
作者：
Ferris, CD;Jaffrey, SR;Snyder, SH
血红素氧合酶-1（HO 1）是一种由应激刺激诱导的热休克蛋白。在这里，我们证明了HO 1的细胞保护作用：由血清剥夺产生的细胞死亡，星形孢菌素或依托泊苷在HO 1基因靶向缺失的小鼠细胞中显着加重，并且在过表达HO 1的细胞中大大减少。铁从细胞流出增加了HO 1转染和减少HO 1缺陷的成纤维细胞，铁在HO 1缺陷的细胞中的积累解释了它们的死亡：铁螯合剂保护HO 1缺陷的成纤维细胞免于细胞死亡。因此，HO 1的细胞保护作用归因于其增强铁流出，反映了HO 1在调节细胞内铁水平和调节细胞活力中的作用。
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.