Hrinczenko B W, Schechter A N, Wojtkowski T L, Pannell L K, Cashon R E, Alayash A I
Laboratory of Chemical Biology and Structural Mass Spectroscopy Group, National Institutes of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA.
Biochem Biophys Res Commun. 2000 Sep 7;275(3):962-7. doi: 10.1006/bbrc.2000.3413.
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 HbA(0), 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 beta(A) and beta(S) chains but not of the alpha 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 beta-globin.
据报道，一氧化氮（NO）可调节镰状细胞病患者（SS）血液的氧亲和力，但对正常成人血液（AA）的氧亲和力无调节作用，且几乎没有或不发生血红素氧化。然而，我们发现NO供体化合物2-（N，N-二乙氨基）-重氮酸-2-氧化物（DEANO）和S-亚硝基半胱氨酸（CysNO）可使AA和SS个体的红细胞氧亲和力增加，同时也会导致大量高铁血红蛋白（metHb）形成。将HbA(0)、AA或SS红细胞与CysNO或DEANO混合进行的快速动力学实验显示出双相时间进程，分别表明最初发生血红素氧化，随后发生血红素还原亚硝基化。经CysNO处理的溶血产物通过电喷雾质谱法显示出一个峰值，对应于β(A)链和β(S)链均增加29个质量单位（与NO结合一致），而α链则无此现象。在镰状细胞病中，NO的治疗应用最终可能需要进一步优化这些相互竞争的反应，即血红素反应性（亚硝基化或氧化）与β-珠蛋白上血红蛋白的直接S-亚硝基化之间的平衡。
