HEME & ENDOTHELIUM EFFECTS OF NITRIC OXIDE ON CATALYTIC IRON

血红素

• 批准号: 6307866
• 负责人: Mark Juckett
• 金额: $ 1.13万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6307866
• 关键词: animal tissue; bioengineering /biomedical engineering; biological products; biomaterials; biomedical resource; enzymes; proteins

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.

变性蛋白质中的血红素加剧氧化损伤 内皮细胞(EC)，因为它的活性铁。作为一种保护 响应，血红素被血红素加氧酶(HO)降解以释放铁 它被铁蛋白以催化失活的形式结合。硝酸盐 氧化物已被证明能诱导HO并抑制铁蛋白的合成 可能会导致催化活性铁的积累，如果血红素 退化是不受阻碍的。我们想知道一氧化氮(NO)是如何 影响血红素的降解和催化活性的释放 铁制的。利用电子自旋共振(ESR)谱，我们发现 游离血红素的亚硝化很容易在内皮细胞中有氧发生 微粒体，但只有很少形成胞浆，没有形成加合物 在媒体方面。我们用电子自旋共振研究了HO对血红素的影响 在没有暴露的情况下会降解。这些实验表明， 血红素的亚硝化很容易发生在细胞中，并积累 在NO存在的情况下，非血红素铁被阻止。亚硝化 血红素在氢暴露的EC细胞毒性检测中具有保护作用 过氧化氢，这表明NO改变了 细胞内的亚铁血红素和过氧化氢。