Nitric Oxide Trickle Drives Heme into Hemoglobin and Muscle Myoglobin.
Nitric Oxide Trickle Drives Heme into Hemoglobin and Muscle Myoglobin.
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自从NO被宣布为“年度分子”以来，这种神奇的气体对球蛋白的分子效应仍然难以捉摸。虽然它在心肺系统和血管系统中的血管舒张作用是公认的，但NO-珠蛋白轴的分子基础还不完全清楚。我们发现，通过transwell共培养的一氧化氮（NO）产生，HEK eNOS/nNOS细胞，和K562红细胞或C2 C12肌成肌细胞，低剂量的NO可以有效地插入血红素血红蛋白（Hb）和肌红蛋白（Mb），使NO不仅是一个血管扩张剂，但也是一个球蛋白血红素触发。我们发现这个过程是依赖于NO流量，发生在低NO剂量和褪色在较高的剂量。这种NO触发的血红素插入在K562细胞中仅在30分钟内发生在Hb中，在C2 C12成肌细胞中在30分钟和1小时之间发生在肌肉Mb中，表明NO对珠蛋白（Hb或Mb）上调的经典作用不是转录的，而是可能涉及足够的翻译事件，其中NO可以导致血红素下载到脱辅基珠蛋白（Hb/Mb）中。NO的这种作用是出乎意料的，并突出了其在维持球蛋白在其含血红素的全息形式中的重要性，其中这种血红素插入可能需要在循环血液或肌肉细胞中执行自发功能。
Ever since the days of NO being proclaimed as the “molecule of the year”, the molecular effects of this miracle gas on the globins have remained elusive. While its vasodilatory role in the cardiopulmonary system and the vasculature is well recognized, the molecular underpinnings of the NO–globin axis are incompletely understood. We show, by transwell co-culture of nitric oxide (NO) generating, HEK eNOS/nNOS cells, and K562 erythroid or C2C12 muscle myoblasts, that low doses of NO can effectively insert heme into hemoglobin (Hb) and myoglobin (Mb), making NO not only a vasodilator, but also a globin heme trigger. We found this process to be dependent on the NO flux, occurring at low NO doses and fading at higher doses. This NO-triggered heme insertion occurred into Hb in just 30 min in K562 cells and into muscle Mb in C2C12 myoblasts between 30 min and 1 h, suggesting that the classical effect of NO on upregulation of globin (Hb or Mb) is just not transcriptional, but may involve sufficient translational events where NO can cause heme-downloading into the apo-globins (Hb/Mb). This effect of NO is unexpected and highlights its significance in maintaining globins in its heme-containing holo-form, where such heme insertions might be required in the circulating blood or in the muscle cells to perform spontaneous functions.
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