Altered membrane structure and surface potential in homozygous hemoglobin C erythrocytes.
Altered membrane structure and surface potential in homozygous hemoglobin C erythrocytes.
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DOI：
10.1371/journal.pone.0005828
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发表时间：
2009-06-08
期刊：
影响因子：
3.7
通讯作者：
Dvorak JA
中科院分区：
文献类型：
--
作者：
Tokumasu F;Nardone GA;Ostera GR;Fairhurst RM;Beaudry SD;Hayakawa E;Dvorak JA
血红蛋白C与正常的血红蛋白A的不同之处在于β-珠蛋白第6位的谷氨酸到赖氨酸的取代，并且是氧化不稳定的。与纯合子AA红细胞相比，纯合子CC红细胞含有更高水平的膜相关半染色质和更广泛的聚集带3蛋白。这些发现提示CC红细胞与AA红细胞具有不同的膜基质。我们发现AA和CC红细胞膜脂质组成不同，并且CC红细胞亚群表达外化磷脂酰丝氨酸水平增加。洗涤剂膜对RAFT标志蛋白的分析表明，CC红细胞膜对洗涤剂增溶的抵抗力更强。这些数据表明CC红细胞的膜筏结构发生了改变。此外，CC红细胞膜的平均Zeta电位(表面电化学势)比AA红细胞膜的平均Zeta电位低≈2 mV，表明CC红细胞膜基质发生了实质性的重排。我们能够通过用NaNO2处理AA红细胞来氧化血红蛋白A分子并增加膜相关半染色质的水平，从而概括了AA红细胞的这种低Zeta电位表型。我们的数据支持半铬沉积增加和脂质组成改变导致CC红细胞膜分子重排的可能性，从而导致独特的膜结构。
Hemoglobin C differs from normal hemoglobin A by a glutamate-to-lysine substitution at position 6 of beta globin and is oxidatively unstable. Compared to homozygous AA erythrocytes, homozygous CC erythrocytes contain higher levels of membrane-associated hemichromes and more extensively clustered band 3 proteins. These findings suggest that CC erythrocytes have a different membrane matrix than AA erythrocytes. We found that AA and CC erythrocytes differ in their membrane lipid composition, and that a subset of CC erythrocytes expresses increased levels of externalized phosphatidylserine. Detergent membrane analyses for raft marker proteins indicated that CC erythrocyte membranes are more resistant to detergent solubilization. These data suggest that membrane raft organization is modified in CC erythrocytes. In addition, the average zeta potential (a measure of surface electrochemical potential) of CC erythrocytes was ≈2 mV lower than that of AA erythrocytes, indicating that substantial rearrangements occur in the membrane matrix of CC erythrocytes. We were able to recapitulate this low zeta potential phenotype in AA erythrocytes by treating them with NaNO2 to oxidize hemoglobin A molecules and increase levels of membrane-associated hemichromes. Our data support the possibility that increased hemichrome deposition and altered lipid composition induce molecular rearrangements in CC erythrocyte membranes, resulting in a unique membrane structure.
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影响因子：
3.8
作者：
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通讯作者：
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