Chen J Y, Huestis W H
Department of Chemistry, Stanford University, CA 94305, USA.
Biochim Biophys Acta. 1997 Jan 31;1323(2):299-309. doi: 10.1016/s0005-2736(96)00197-6.
This is a study of the morphology and transbilayer lipid distribution of human erythrocytes treated with chlorpromazine (CPZ) over extended time courses. At 0 degree C, treatment of dilauroylphosphatidyl[1-14C]choline-labeled erythrocytes with 120 microM CPZ produced an immediate stomatocytic transformation (t1/2 < 5 min) with no concurrent change in transbilayer distribution of radiolabeled lipid, as determined by bovine serum albumin extractability. At 37 degrees C, CPZ treatment of cells produced two sequential morphological effects: immediate stomatocytosis (t1/2 < 1 min) with no concurrent change in radiolabel transbilayer distribution, followed by gradual increase in stomatocytic extent over several hours, with concurrent redistribution of radiolabeled lipid to the inner monolayer. Cells pretreated with vanadate at 37 degrees C exhibited a triphasic morphological response: CPZ produced immediate stomatocytosis, followed by a transient reversion to echinocytes lasting about 2 h, before returning to stomatocytic morphologies over the next several hours. The echinocytic reversion was accompanied by exposure of phosphatidylserine on the cell surface, as indicated by increased activation of exogenous prothrombinase. These findings suggest that while CPZ induces transbilayer lipid redistribution over extended time periods (which may mediate the complex morphological transformations observed), the early stomatocytic response elicited by addition of CPZ is not due to lipid reorganization.
这是一项关于在延长的时间过程中用氯丙嗪（CPZ）处理的人红细胞的形态学和跨膜脂质分布的研究。在0℃下，用120μM CPZ处理二月桂酰磷脂酰[1-14C]胆碱标记的红细胞会立即产生口形细胞转变（t1/2 < 5分钟），通过牛血清白蛋白提取率测定，放射性标记脂质的跨膜分布没有同时发生变化。在37℃下，CPZ处理细胞产生两种连续的形态学效应：立即出现口形细胞增多（t1/2 < 1分钟），放射性标记的跨膜分布没有同时发生变化，随后在数小时内口形细胞程度逐渐增加，同时放射性标记的脂质重新分布到内层单分子层。在37℃下用钒酸盐预处理的细胞表现出三相形态学反应：CPZ立即产生口形细胞增多，随后短暂恢复为棘形细胞，持续约2小时，然后在接下来的几个小时内恢复为口形细胞形态。棘形细胞的恢复伴随着细胞表面磷脂酰丝氨酸的暴露，这通过外源性凝血酶原激活物的激活增加来表明。这些发现表明，虽然CPZ在延长的时间段内诱导跨膜脂质重新分布（这可能介导观察到的复杂形态学转变），但添加CPZ引发的早期口形细胞反应不是由于脂质重组。
