OXIDANT DAMAGE OF THE LIPIDS AND PROTEINS OF THE ERYTHROCYTE-MEMBRANES IN UNSTABLE HEMOGLOBIN DISEASE - EVIDENCE FOR THE ROLE OF LIPID-PEROXIDATION
OXIDANT DAMAGE OF THE LIPIDS AND PROTEINS OF THE ERYTHROCYTE-MEMBRANES IN UNSTABLE HEMOGLOBIN DISEASE - EVIDENCE FOR THE ROLE OF LIPID-PEROXIDATION
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DOI：
10.1172/jci110870
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发表时间：
1983-01-01
影响因子：
15.9
通讯作者：
WHITE, JG
中科院分区：
文献类型：
--
作者：
FLYNN, TP;ALLEN, DW;WHITE, JG
由于不稳定的Hb被认为是活性氧自由基的来源，氧化膜损伤是溶血前事件，因此检查了6例Hb科隆病患者（3例脾切除）的红细胞膜。在H2O2应激试验中，患者红细胞产生的丙二醛（一种脂质过氧化产物）是对照红细胞的两倍多。患者红细胞的脂质提取物的荧光光谱显示在400 nm处的激发最大值和在460 nm处的发射最大值，这是丙二醛脂质加合物的特征。两种类型的膜多肽聚集体中发现的脾切除患者的红细胞。第一，这是解离与巯基乙醇处理，含有二硫键连接血影蛋白，带3和珠蛋白。第二种不能被巯基乙醇分解，其氨基酸组成类似于红细胞膜和血影蛋白（与珠蛋白不同），并且类似于由丙二醛作用于正常红细胞膜而产生的聚集体。Hb科隆红细胞的原子吸收光谱显示钙含量没有增加，这意味着这些交联不是由于钙刺激的转氨酶。使用微量移液器技术，从脾切除患者的红细胞含有膜聚集体被证明是不太变形，而聚集体从非脾切除患者的红细胞具有正常的变形性。Hb科隆病的红细胞膜明显显示脂质过氧化的证据，并产生丙二醛，在这种疾病中形成的不可解离的膜聚集体可能是由丙二醛交联的。因为来自患有不稳定Hb疾病的脾切除患者的含有膜聚集体的红细胞显示出降低的膜变形性，所以这种异常明显导致体内过早的红细胞破坏。
Since unstable Hb were considered a source of reactive O2 radicals, and oxidative membrane damage a prehemolytic event, the erythrocyte membranes of 6 patients (3 splenectomized) with Hb Koeln disease were examined. In the H2O2 stress test, the patients'' erythrocytes generated more than twice as much malonyldialdehyde (a lipid peroxidative product) as control erythrocytes. Fluorescence spectra of lipid extracts of the patients'' erythrocytes showed an excitation maximum at 400 nm and an emission maximum of 460 nm, characteristic of malonyldialdehyde lipid adducts. Two types of membrane polypeptide aggregates were found in the erythrocytes of the splenectomized patients. The 1st, which were dissociable by treatment with mercaptoethanol, contained disulfide-linked spectrin, band 3 and globin. The 2nd, not dissociable by mercaptoethanol, had an amino acid composition similar to that of erythrocyte membranes and spectrin (unlike globin) and like that of aggregates produced by the action of malonyldialdehyde on normal erythrocyte membranes. Atomic absorption spectroscopy of Hb Koeln erythrocytes showed no increase in Ca content, implying that these cross-links were not due to Ca-stimulated transglutaminase. Using a micropipette technique, erythrocytes containing membrane aggregates from splenectomized patients were demonstrated to be less deformable while aggregate-free erythrocytes from non-splenectomized patients had normal deformability. The erythrocyte membranes in Hb Koeln disease apparently show evidence of lipid peroxidation with production of malonyldialdehyde, and the nondissociable membrane aggregates formed in this disease are likely cross-linked by malonyldialdehyde. Because the erythrocytes containing membrane aggregates from splenectomized patients with unstable Hb disease show decreased membrane deformability, this abnormality apparently results in premature erythrocyte destruction in vivo.