CONTROL OF HEME AND RELEASE OF ACTIVE IRON

我们研究了一氧化氮(NO)在控制血管紧张素转换酶的作用。 过量的细胞血红素和催化活性铁的释放。 内皮细胞(ECs)暴露于氯化高铁血红素后，NO供体有 铁蛋白含量是单独接触氯化血红素的细胞的16%。 经海宁处理的内皮细胞中非血红素的催化活性增加3.5倍 铁2小时后，但20小时后重新挑战氯化血红素的结果只有24% 增加。在第一次接触氯化高铁血红素后添加NO供体 阻止这种适应性反应，可能会对铁蛋白产生影响 综合。没有发现捐赠者可以减少氯化血红素中的铁释放， 而氯化血红素则在细胞内积累。一种一氧化氮供体，在剂量依赖的情况下 时尚，抑制血红素加氧酶活性，胆红素测定 制作。利用低温EPR波谱，血红素加氧酶 抑制与微粒体内游离血红素的亚硝化有关。 细胞内的亚硝化血红素阻止了铁的释放，因为 细胞中的铁依赖于血红素加氧酶吗？ 氯化血红素作用24 h后，加入NO供体可阻断铁的释放。这 表明NO很容易在细胞内生成游离态的血红素和 通过血红素加氧酶防止其降解。血红素的亚硝化反应是 发现可以降低细胞对氧化损伤的敏感度。

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.