CONTROL OF HEME AND RELEASE OF ACTIVE IRON

我们研究了一氧化氮（NO）在控制 过量的细胞血红素和催化活性铁的释放。 内皮细胞（Ecs）暴露于氯化血红素，然后是NO供体， 铁蛋白含量是单独暴露于氯化血红素的细胞的16%。 海宁处理的内皮细胞经历了3.5倍的非血红素，催化 铁，但氯化血红素再激发20小时后，结果只有24%， 增加 在第一次氯化血红素暴露后添加NO供体 阻止了这种适应性反应，可能是由于铁蛋白的作用而死亡。 合成. 没有发现供体减少氯化血红素的铁释放， 而氯高铁血红素在细胞中积累。 一个NO供体，在剂量依赖性 方式，抑制血红素加氧酶活性，通过胆红素测定 生产 使用低温EPR光谱，血红素加氧酶 抑制与微粒体中游离血红素的亚硝基化有关。 细胞血红素的亚硝基化阻止了铁的释放， 是血红素氧合酶依赖的铁释放酶， 氯化血红素作用24 h后，NO供体的加入阻断了铁的释放。 这 表明NO容易亚硝基化细胞内游离血红素， 防止血红素氧合酶降解。 血红素的亚硝基化反应 发现减少细胞对氧化损伤的敏感性。

We studied the effects of nitric oxide (NO) on the control of excess cellular heme and release of catalytically active iron. Endothelial cells (Ecs) exposed to hemin followed by a NO donor have a ferritin content that is 16% that of cells exposed to hemin alone. Henin-treated ECs experience a 3.5-fold rise in non-heme, catalytic iron 2h later, but a hemin rechallenge 20h later results in only a 24% increase. The addition of a NO donor after the first hemin exposure prevents this adaptive response, presumable die to effects on ferritin synthesis. NO donors were found to reduce iron release from hemin, while hemin accumulated in cells. A NO donor, in a dose-dependent fashion, inhibited heme oxygenase activity, measured by bilirubin production. Using low temperature EPR spectroscopy, heme oxygenase inhibition correlated with nitrosylation of free heme in microsomes. Nitrosylation of cellular heme prevented iron release, for while there was heme oxygenase-dependent rele ase of iron in cells incubated with hemin for 24 h, the addition of a NO donor blocked iron release. This indicates that NO readily nitrosylates intracellular free heme and prevents its degradation by heme oxygenase. Nitrosylation of heme was found to reduce sensitization of cells to oxidative injury.