The effect of cholesterol and other intercalated amphipaths on the contour and stability of the isolated red cell membrane.
The effect of cholesterol and other intercalated amphipaths on the contour and stability of the isolated red cell membrane.
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DOI：
10.1016/s0021-9258(19)70566-3
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发表时间：
1980-10
期刊：
影响因子：
--
通讯作者：
Y. Lange;H. B. Cutler;T. Steck
中科院分区：
文献类型：
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作者：
Y. Lange;H. B. Cutler;T. Steck
当人红细胞的胆固醇（通常约为0.8 mol/mol磷脂（即C/P约为0.8））通过与适当胆固醇含量的磷脂分散体平衡而改变时，三种膜性质受到显著影响。1)虽然C/P小于或等于0.8的完整红细胞膜中的甾醇对胆固醇氧化酶消化具有抗性，但C/P大于或等于0.9的富集使得整个胆固醇池对酶攻击敏感。通过去除过量的胆固醇逆转了对氧化的敏感性。用1 × 10（-4）M氯丙嗪处理细胞也使整个胆固醇池对胆固醇氧化酶敏感。2)而鬼与C/P小于或等于0.8进行内陷在低离子强度，碱性缓冲液，以形成由内而外的囊泡，富集到C/P大于或等于1.0促进右侧外囊泡的形成。用2，4-二硝基苯酚（一种已知可引起红细胞膜外翻的两亲分子）处理可模拟这种效应。与此相反，氯丙嗪的存在，促进完整的红细胞膜的内陷，有利于形成由内而外的囊泡在鬼。3)在稀的碱性介质中，血影蛋白和肌动蛋白的膜下网状物的分解和溶解被过量的胆固醇阻滞，并被其去除所促进。这种胆固醇效应通过将鬼魂暴露于氯丙嗪而不是二硝基苯酚来模拟。我们的数据表明，胆固醇可能在生理上起作用，以稳定红细胞膜，并限制其轮廓对内陷，红细胞膜胆固醇在体内维持在低于一个临界水平，在该水平下可能发生重要的组织变化。
Three membrane properties were strikingly affected when the cholesterol of human erythrocytes, normally approximately 0.8 mol/mol of phospholipid (i.e. C/P approximately 0.8), was altered by equilibration with phospholipid dispersions of an appropriate cholesterol content. 1) While the sterol in intact red cell membranes of C/P less than or equal to 0.8 was resistant to cholesterol oxidase digestion, enrichment to C/P greater than or equal to 0.9 rendered the entire cholesterol pool sensitive to enzyme attack. Susceptibility to oxidation was reversed by removal of the excess cholesterol. Treatment of cells with 1 X 10(-4) M chlorpromazine also rendered the entire cholesterol pool susceptible to cholesterol oxidase. 2) Whereas ghosts with C/P less than or equal to 0.8 underwent invagination in low ionic strength, alkaline buffers to form inside-out vesicles, enrichment to C/P greater than or equal to 1.0 promoted right-side-out vesicle formation instead. This effect was mimicked by treatment with 2,4-dinitrophenol, an amphipath known to cause eversion of the membrane of red cells. In contrast, the presence of chlorpromazine, which promotes invagination of the intact red cell membrane, favored the formation of inside-out vesicles in ghosts. 3) The breakdown of ghosts into endocytic vesicles in dilute, alkaline media and the concomitant release and dissolution of the submembrane reticulum of spectrin and actin were retarded by excess cholesterol and promoted by its removal. This cholesterol effect was mimicked by exposing ghosts to chlorpromazine, but not dinitrophenol. Our data suggest that cholesterol may act physiologically both to stabilize the red cell membrane and to constrain its contour against invagination, and that red cell membrane cholesterol is maintained in vivo just below a critical level at which important organizational changes can occur.