Oxidative stress and phosphatidylserine exposure in red cells from patients with sickle cell anaemia.
Oxidative stress and phosphatidylserine exposure in red cells from patients with sickle cell anaemia.
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DOI：
10.1111/bjh.15441
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发表时间：
2018-08
影响因子：
6.5
通讯作者：
Gibson JS
中科院分区：
文献类型：
--
作者：
Hannemann A;Rees DC;Brewin JN;Noe A;Low B;Gibson JS
磷脂酰丝氨酸（PS）暴露随着红细胞老化而增加，并且是从循环中去除衰老细胞的重要信号。镰状细胞性贫血（SCA）患者红细胞中的PS暴露量升高，并被认为会增强溶血和血管闭塞。虽然导致其外化的确切条件尚不清楚，但高细胞内Ca 2+已被牵连。SCA患者的红细胞也暴露于增加的氧化挑战，我们假设这通过增加Ca 2+水平刺激PS暴露。我们测试了产生氧化应激的四种不同方式：次黄嘌呤和黄嘌呤氧化酶、吩嗪硫酸甲酯、亚硝酸盐和叔丁基过氧化氢，以及用N-乙基马来酰亚胺（NEM）、二硫苏糖醇和次氯酸（HOCl）进行的巯基修饰，在使用溴-A23187渗透Ca 2+的红细胞中。出乎意料的是，我们的研究结果表明，四种氧化剂显著降低了Ca 2+诱导的PS暴露（40-60%），对Ca 2+亲和力没有明显影响。相比之下，NEM显着增加PS曝光（约400%）和轻微，但显着增加了对Ca 2+的亲和力。二硫苏糖醇适度降低PS暴露（25%），HOCl没有影响。这些研究结果强调了巯基修饰对镰状细胞PS暴露的重要性，但表明单独增加氧化应激并不重要。
Phosphatidylserine (PS) exposure increases as red cells age, and is an important signal for the removal of senescent cells from the circulation. PS exposure is elevated in red cells from sickle cell anaemia (SCA) patients and is thought to enhance haemolysis and vaso‐occlusion. Although precise conditions leading to its externalisation are unclear, high intracellular Ca2+ has been implicated. Red cells from SCA patients are also exposed to an increased oxidative challenge, and we postulated that this stimulates PS exposure, through increased Ca2+ levels. We tested four different ways of generating oxidative stress: hypoxanthine and xanthine oxidase, phenazine methosulphate, nitrite and tert‐butyl hydroperoxide, together with thiol modification with N‐ethylmaleimide (NEM), dithiothreitol and hypochlorous acid (HOCl), in red cells permeabilised to Ca2+ using bromo‐A23187. Unexpectedly, our findings showed that the four oxidants significantly reduced Ca2+‐induced PS exposure (by 40–60%) with no appreciable effect on Ca2+ affinity. By contrast, NEM markedly increased PS exposure (by about 400%) and slightly but significantly increased the affinity for Ca2+. Dithiothreitol modestly reduced PS exposure (by 25%) and HOCl had no effect. These findings emphasise the importance of thiol modification for PS exposure in sickle cells but suggest that increased oxidant stress alone is not important.
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