An S-nitrosothiol (SNO) synthase function of hemoglobin that utilizes nitrite as a substrate
An S-nitrosothiol (SNO) synthase function of hemoglobin that utilizes nitrite as a substrate
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DOI：
10.1073/pnas.0600942103
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发表时间：
2006-05-30
影响因子：
11.1
通讯作者：
Stamler, Jonathan S.
中科院分区：
文献类型：
--
作者：
Angelo, Michael;Singel, David J.;Stamler, Jonathan S.
红细胞（RBC）通过调节一氧化氮（NO）的可用性，在肺和组织中充当血管舒张和血管收缩活性的O-2响应性换能器。在以低氧血症为特征的疾病中，红细胞的血管舒缩作用会受损。我们已经提出，红细胞收缩血管与扩张血管的程度至少部分地由与血红素铁结合的NO和与血红蛋白（Hb）的Cys β 93硫醇结合的NO之间的分配控制。血红素螯合NO，而硫醇发挥NO生物活性。在最近的工作中，我们提出，特定的微群体的NO-配体血红蛋白可以支持化学的S-亚硝基血红蛋白（SNO-Hb）的形成。在这里，通过使用亚硝酸盐作为NO的来源，我们证明了（T状态）的血红素-NO物种，与光谱和化学性质的Fe（III）NO的微种群，作为前体SNO-Hb形成，伴随着Hb的变构过渡到R状态。我们还表明，在生理浓度的亚硝酸盐和deoxyHb，S-亚硝基硫醇前体在几秒钟内形成，并产生SNO-Hb在其迅速暴露于O-2或CO的高产率。脱氧/复氧循环的oxyHb在存在的生理量的亚硝酸盐也有效地产生SNO-Hb。相反，大量的亚硝酸盐或延迟复氧抑制SNO-Hb的产生。总的来说，我们的数据提供了证据的生理S-亚硝基硫醇合酶活性的四聚体血红蛋白，取决于NO-Hb微种群，并表明，这种活动的功能障碍可能有助于心肺和血液疾病的病理生理。
Red blood cells (RBCs) act as O-2-responsive transducers of vasodilator and vasoconstrictor activity in lungs and tissues by regulating the availability of nitric oxide (NO). Vasoclilation by RBCs is impaired in diseases characterized by hypoxemia. We have proposed that the extent to which RBCs constrict vs. dilate vessels is, at least partly, controlled by a partitioning between NO bound to heme iron and to Cys beta 93 thiol of hemoglobin (Hb). Hemes sequester NO, whereas thiols deploy NO bioactivity. In recent work, we have suggested that specific micropopulations of NO-liganded Hb could support the chemistry of S-nitrosohemoglobin (SNO-Hb) formation. Here, by using nitrite as the source of NO, we demonstrate that a (T state) micropopulation of a heme-NO species, with spectral and chemical properties of Fe(III)NO, acts as a precursor to SNO-Hb formation, accompanying the allosteric transition of Hb to the R state. We also show that at physiological concentrations of nitrite and deoxyHb, a S-nitrosothiol precursor is formed within seconds and produces SNO-Hb in high yield upon its prompt exposure to O-2 or CO. Deoxygenation/reoxygenation cycling of oxyHb in the presence of physiological amounts of nitrite also efficiently produces SNO-Hb. In contrast, high amounts of nitrite or delays in reoxygenation inhibit the production of SNO-Hb. Collectively, our data provide evidence for a physiological S-nitrosothiol synthase activity of tetrameric Hb that depends on NO-Hb micropopulations and suggest that dysfunction of this activity may contribute to the pathophysiology of cardiopulmonary and blood disorders.