The efficacy of reducing agents or antioxidants in blocking the formation of dense cells and irreversibly sickled cells in vitro
The efficacy of reducing agents or antioxidants in blocking the formation of dense cells and irreversibly sickled cells in vitro
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DOI：
10.1182/blood.v91.11.4373.411k37_4373_4378
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发表时间：
1998-06-01
期刊：
影响因子：
20.3
通讯作者：
Goodman, SR
中科院分区：
文献类型：
--
作者：
Gibson, XA;Shartava, A;Goodman, SR
我们发现，N-乙酰半胱氨酸(NAC)在浓度大于250 mU/L时，能够显著减少体外培养的不可逆镰状细胞(ISCs)的形成。其他被批准用于人类使用的抗氧化剂(半胱胺、琥珀酸、二硫丙醇)则无效。NAC有能力使体内形成的ISCs在统计学上显着地转换回双凹形状。NAC还可以减少致密细胞的形成，增加β-肌动蛋白中可用硫醇的含量。我们发现，用1-氯-2，4-二硝基苯处理减少还原型谷胱甘肽(GSH)会导致细胞密度增加。我们得出结论，NAC通过分别靶向细胞脱水和β-肌动蛋白途径来阻止致密细胞的形成和ISC的形成，NAC的疗效可能是由于其结合了抗氧化活性和增加细胞内GSH的能力。(C)1998年由美国血液病学会主办。
We show that N-acetylcysteine (NAC) has the ability to cause statistically significant diminishment in the in vitro formation of irreversibly sickled cells (ISCs) at concentrations greater than 250 mu mol/L. Other antioxidants, approved for human use (cysteamine, succimer, dimercaprol), were not efficacious. NAC had the ability to cause statistically significant conversion of ISCs formed in vivo back to the biconcave shape. NAC was also shown to reduce the formation of dense cells and increase the available thiols in beta-actin. We showed that diminishing reduced glutathione (GSH), by treatment with 1-chloro-2,4-dinitrobenzene, resulted in increased dense cells. We conclude the NAC blocks dense cell formation and ISC formation by targeting channels involved in cellular dehydration and beta-actin, respectively, The efficacy of NAC is probably due to its combined antioxidant activity and ability to increase intracellular GSH. (C) 1998 by The American Society of Hematology.