HEME & ENDOTHELIUM EFFECTS OF NITRIC OXIDE ON CATALYTIC IRON

来自变性蛋白质的血红素加剧氧化损伤， 内皮细胞（EC），因为它的活性铁。 作为保护 反应时，血红素被血红素加氧酶（HO）降解，释放铁 其被无催化活性形式的铁蛋白结合。 硝酸 氧化物已显示诱导HO和抑制铁蛋白合成， 可能导致催化活性铁的积累， 降解不受阻碍。 我们想知道一氧化氮（NO）如何 影响血红素的降解和催化活性物质的释放 铁. 使用电子自旋共振（ESR）光谱，我们发现， 游离血红素的亚硝基化容易在内皮细胞中有氧发生， 微粒体，但只有很少的形成细胞质，没有形成加合物 在媒体。 我们用电子自旋共振（ESR）研究了血红素氧合酶（HO）对血红素的影响 在NO暴露期间降解。 这些实验表明， 血红素的亚硝基化在细胞中容易发生， 在NO存在下，非血红素铁被阻止。 血红素在暴露于氢的EC的细胞毒性试验中具有保护作用 过氧化物，这表明NO改变了 细胞内血红素和过氧化物。

Heme from denatured proteins exacerbates oxidative injury to endothelial cells (EC) because of its reactive iron. As a protective response, heme is degraded by heme oxygenase (HO) to release iron which is bound by ferritin in a catalytically inactive form. Nitric oxide has been shown to induce HO and repress ferritin synthesis which could result in accumulation of catalytically active iron if heme degradation was unimpeded. We wondered how nitric oxide (NO) might affect the degradation of heme and release of catalytically active iron. Using electron spin resonance (ESR) spectroscopy, we found that nitrosylation of free heme readily occurs aerobically in endothelial microsomes but only little is formed to cytosol and no adducts formed in media. We used ESR to investigate the influence of HO on heme degradation during NO exposure. These experiments showed that nitrosylation of heme readily occurs in cells, and accumulation of non-heme iron is prevented in the presence of NO. Nitrosylation of heme was protective in cytotoxicity assays of EC exposed to hydrogen peroxide, suggesting that NO alters the interaction between intracellular heme and peroxides.