Scrambling of phospholipids activates red cell membrane cholesterol.
Scrambling of phospholipids activates red cell membrane cholesterol.
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DOI：
10.1021/bi6023397
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发表时间：
2007-02
期刊：
影响因子：
2.9
通讯作者：
Y. Lange;Jin Ye;T. Steck
中科院分区：
文献类型：
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作者：
Y. Lange;Jin Ye;T. Steck
根据其磷脂的相对体外亲和力，预计胆固醇与质膜双层的外部小叶的结合比内部小叶的结合更强烈。据说与高亲和力物质（尤其是饱和鞘磷脂）形成复合物会降低甾醇的化学活性（逃逸潜力或逸度）。因此，我们测试了这样的假设：扰乱完整细胞质膜磷脂的侧面会增加外表面胆固醇的化学活性。通过引入离子霉素提高细胞质 Ca++ 来激活完整人红细胞中的质膜扰乱酶后，磷脂酰丝氨酸暴露出来，同时面外胆固醇的化学活性增加。 （这是通过其对胆固醇氧化酶的敏感性及其向环糊精的转移率来衡量的。）在人类成纤维细胞中也观察到了类似的行为。另外两种已知可激活细胞表面胆固醇的处理（即暴露于戊二醛和低离子强度缓冲液）也将磷脂酰丝氨酸带到细胞表面，但通过不依赖于 Ca++ 的机制。鉴于磷脂扰乱在血液凝固和细胞凋亡中很重要，细胞表面胆固醇的伴随激活可能有助于这些和其他病理生理信号传导过程。
Cholesterol is predicted to associate more strongly with the outer than the inner leaflet of plasma membrane bilayers based on the relative in vitro affinities of their phospholipids. Complex formation with the high-affinity species (especially saturated sphingomyelins) is said to reduce the chemical activity (escape potential or fugacity) of the sterol. We therefore tested the hypothesis that scrambling the sidedness of plasma membrane phospholipids of intact cells will increase the chemical activity of outer surface cholesterol. Upon activating the plasma membrane scramblase in intact human red cells by introducing ionomycin to raise cytoplasmic Ca++, phosphatidylserine became exposed and, concomitantly, the chemical activity of exofacial cholesterol was increased. (This was gauged by its susceptibility to cholesterol oxidase and its rate of transfer to cyclodextrin.) Similar behavior was observed in human fibroblasts. Two other treatments known to activate cell surface cholesterol (namely, exposure to glutaraldehyde and to low-ionic-strength buffer) also brought phosphatidylserine to the cell surface but by a Ca++-independent mechanism. Given that phospholipid scrambling is important in blood coagulation and apoptosis, the concomitant activation of cell surface cholesterol could contribute to these and other pathophysiological signaling processes.