Suicidal Erythrocyte Death Following Cellular K+ Loss
Suicidal Erythrocyte Death Following Cellular K+ Loss
复制标题
DOI：
10.1159/000104151
复制
发表时间：
2006-01
影响因子：
--
通讯作者：
J. Schneider;J. Nicolay;M. Föller;T. Wieder;F. Lang
中科院分区：
文献类型：
--
作者：
J. Schneider;J. Nicolay;M. Föller;T. Wieder;F. Lang
细胞凋亡的标志包括细胞收缩，这至少部分是由于细胞 K+ 损失所致。细胞 K+ 浓度的下降被认为参与了细胞凋亡的触发。自杀性红细胞死亡或红细胞死亡是由胞质 Ca2+ 活性增加引发的，导致 Ca2+ 敏感的 K+ 通道激活，随后细胞 K+ 丢失和细胞收缩，并导致细胞膜 Ca2+ 敏感的混乱，随后细胞表面的磷脂酰丝氨酸 (PS) 暴露。暴露于磷脂酰丝氨酸的红细胞被巨噬细胞识别、吞噬、降解，从而从循环血液中清除。本研究探讨了 K+ 的细胞丢失和/或细胞收缩是否主动参与了细胞膜磷脂扰乱的触发。通过在不同的细胞外 K+ 浓度 (5-125 mM) 和渗透压 (300-550m Osm) 下用 K+ 离子载体缬氨霉素 (1 nM) 处理人红细胞，实现细胞 K+ 损失。通过 FACS 分析中膜联蛋白 V 结合的前向散射和 PS 暴露来估计细胞体积。用 1 nM 缬氨霉素处理确实减少了前向散射并增加了膜联蛋白 V 结合。当星形孢菌素 (1 µM) 存在时，该效果显着减弱。细胞外 K+ 浓度的增加逐渐减弱前向散射的减少，但仅在细胞外 K+ 浓度为 75 mM 时抑制膜联蛋白 V 结合。缬氨霉素治疗期间，细胞外渗透压（+150 mM 或 250 mM 蔗糖）的增加逆转了 75 mM KCl 的保护作用。不同渗透压和 K+ 浓度下的前向散射和膜联蛋白结合之间的相关性表明，细胞 K+ 含量主要通过其对细胞体积的影响来决定自杀性红细胞死亡率。
Hallmarks of apoptosis include cell shrinkage, which is at least partially due to cellular K+ loss. The decline of cellular K+ concentration has been suggested to participate in the triggering of apoptosis. Suicidal erythrocyte death or eryptosis is triggered by increased cytosolic Ca2+ activity leading to activation of Ca2+-sensitive K+ channels with subsequent cellular K+ loss and cell shrinkage, and to Ca2+-sensitive scambling of the cell membrane with subsequent phosphatidylserine (PS) exposure at the cell surface. Phosphatidylserine exposing erythrocytes are recognized by macrophages, engulfed, degraded and thus cleared from circulating blood. The present study explored whether cellular loss of K+ and/or cell shrinkage actively participate in the triggering of cell membrane phospholipid scrambling. Cellular K+ loss was achieved by treatment of human erythrocytes with the K+ ionophore valinomycin (1 nM) at different extracellular K+ concentrations (5-125 mM) and osmolarities (300-550m Osm). Cell volume was estimated from forward scatter and PS exposure from annexin V binding in FACS analysis. Treatment with 1 nM valinomycin indeed decreased forward scatter and increased annexin V binding. The effect was significantly blunted in the presence of staurosporine (1 µM). Increase of extracellular K+ concentration gradually blunted the decrease of forward scatter but inhibited annexin V binding only at extracellular K+ concentrations ??75 mM. An increase of extracellular osmolarity (+150 mM or 250 mM sucrose) reversed the protective effect of 75 mM KCl during valinomycin treatment. A correlation between forward scatter and annexin binding at different osmolarities and K+ concentrations suggests that the cellular K+ content determines the rate of suicidal erythrocyte death primarily through its influence on cell volume.