Nitric oxide-mediated heme oxidation and selective beta-globin nitrosation of hemoglobin from normal and sickle erythrocytes.
Nitric oxide-mediated heme oxidation and selective beta-globin nitrosation of hemoglobin from normal and sickle erythrocytes.
复制标题
一氧化氮介导的血红素氧化和正常红细胞和镰状红细胞血红蛋白的选择性β-珠蛋白亚硝化。
DOI：
10.1006/bbrc.2000.3413
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发表时间：
2000
影响因子：
3.1
通讯作者：
Alayash,AI
中科院分区：
文献类型：
--
作者：
Hrinczenko,BW;Schechter,AN;Wojtkowski,TL;Pannell,LK;Cashon,RE;Alayash,AI
据报道，一氧化氮（NO）可以调节镰状细胞患者（SS）血液的氧亲和力，但不能调节正常成人血液（AA）的氧亲和力，血红素氧化很少或没有。然而，我们发现NO供体化合物2-(N,N-二乙基氨基)-二氮烯醇酯-2-氧化物(DEANO)和S-亚硝基半胱氨酸(CysNO)导致AA和SS个体红细胞的氧亲和力增加，并且还导致显着的高铁血红蛋白(metHb)形成。 HbA0、AA 或 SS 红细胞与 CysNO 或 DEANO 混合的快速动力学实验显示出双相时间过程，分别表明初始血红素氧化，随后是还原血红素亚硝基化。用 CysNO 处理的溶血产物通过电喷雾质谱显示出对应于 βA 和 βS 链而非 α 链的 29 个质量单位增加（与 NO 结合一致）的峰。 NO 在镰状细胞病中的治疗用途最终可能需要进一步优化这些竞争反应，即血红素反应性（亚硝基化或氧化）与血红蛋白在 β-珠蛋白上的直接 S-亚硝化。
Nitric oxide (NO) has been reported to modulate the oxygen affinity of blood from sickle cell patients (SS), but not that of normal adult blood (AA), with little or no heme oxidation. However, we had found that the NO donor compounds 2-(N,N-diethylamino)-diazenolate-2-oxide (DEANO) and S-nitrosocysteine (CysNO) caused increased oxygen affinity of red cells from both AA and SS individuals and also caused significant methemoglobin (metHb) formation. Rapid kinetic experiments in which HbA0, AA, or SS erythrocytes were mixed with CysNO or DEANO showed biphasic time courses indicative of initial heme oxidation followed by reductive heme nitrosylation, respectively. Hemolysates treated with CysNO showed by electrospray mass spectrometry a peak corresponding to a 29 mass unit increase (consistent with NO binding) of both the βAand βSchains but not of the α chains. Therapeutic use of NO in sickle cell disease may ultimately require further optimization of these competing reactions, i.e., heme reactivity (nitrosylation or oxidation) versus direct S-nitrosation of hemoglobin on the β-globin.