Kvam E, Hejmadi V, Ryter S, Pourzand C, Tyrrell R M
The Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom.
Free Radic Biol Med. 2000 Apr 15;28(8):1191-6. doi: 10.1016/s0891-5849(00)00205-7.
Heme oxygenase (HO) breaks down heme to iron, biliverdin, and carbon monoxide, and activity of this enzyme increases in many tissues and cell types after exposure to oxidative stress. There is evidence that increased HO activity is involved in long-term protective mechanisms against oxidative stress. We studied the effect of artificially overexpressed HO activity on the cytotoxicity of oxidative ultraviolet A (UVA) radiation after loading human cells with the HO substrate ferric heme (hemin). In contrast to the reported long-term protection attributed to HO activity, cells overexpressing HO activity were hypersensitive to UVA radiation shortly after heme treatment when compared with control cells. Cells overexpressing HO activity showed an increased rate of heme consumption and a higher level of accumulated free chelatable iron when compared with control cells. The hypersensitivity of cells overexpressing HO to UVA radiation after heme treatment was apparently caused by the increased accumulation of chelatable iron, because the iron chelator desferrioxamine strongly reduced the hypersensitivity. One day after the heme treatment, cells overexpressing HO activity were no longer hypersensitive to UVA radiation. We conclude that increased HO activity can temporarily increase the sensitivity of cells to oxidative stress by releasing iron from heme.
血红素加氧酶（HO）可将血红素分解为铁、胆绿素和一氧化碳，在暴露于氧化应激后，该酶在许多组织和细胞类型中的活性会增加。有证据表明，HO活性增加参与了对抗氧化应激的长期保护机制。我们研究了在用HO底物血红素（氯高铁血红素）加载人类细胞后，人工过度表达的HO活性对氧化紫外线A（UVA）辐射细胞毒性的影响。与报道的HO活性带来的长期保护作用相反，与对照细胞相比，在血红素处理后不久，过度表达HO活性的细胞对UVA辐射高度敏感。与对照细胞相比，过度表达HO活性的细胞显示出血红素消耗率增加和可积累的游离可螯合铁水平更高。血红素处理后，过度表达HO的细胞对UVA辐射的高度敏感性显然是由可螯合铁积累增加引起的，因为铁螯合剂去铁胺强烈降低了这种高度敏感性。血红素处理一天后，过度表达HO活性的细胞对UVA辐射不再高度敏感。我们得出结论，HO活性增加可通过从血红素中释放铁而暂时增加细胞对氧化应激的敏感性。
