Enhanced susceptibility to erythrocyte "apoptosis" following phosphate depletion
Enhanced susceptibility to erythrocyte "apoptosis" following phosphate depletion
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DOI：
10.1007/s00424-004-1289-y
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发表时间：
2004-08-01
影响因子：
4.5
通讯作者：
Lang, F
中科院分区：
文献类型：
--
作者：
Birka, C;Lang, PA;Lang, F
磷酸盐耗竭的后遗症之一是贫血，部分原因是成熟红细胞的寿命缩短。最近的研究表明，细胞应激导致红细胞胞浆内钙离子活性增加，从而引发细胞收缩和细胞膜磷脂酰丝氨酸不对称的破坏，这两个典型的细胞凋亡特征。在本实验中，磷脂酰丝氨酸暴露和细胞大小分别通过膜联蛋白结合和前向散射的荧光激活细胞分类(FACS)分析来测量。将完整小鼠的红细胞与暴露于低磷饮食4天的小鼠的红细胞进行比较。低磷饮食使新鲜提取的红细胞的膜联蛋白结合量略有增加，但显著增加。此外，这些红细胞内的磷酸盐和三磷酸腺苷浓度显著降低，而细胞内钙的活性没有改变。渗透压休克(加入蔗糖700mOsm作用12h)、去除氯离子(用葡萄糖酸盐代替15h)或去除葡萄糖(12h)使细胞体积减小，与膜联蛋白结合的红细胞数量增加。有趣的是，这些影响在磷酸盐耗竭动物的红细胞中明显更大。实验揭示了一种由磷酸盐耗竭引发的新机制，推测这可能有助于增强红细胞的脆弱性和加速红细胞的隔离，从而导致贫血。
Among the sequelae of phosphate depletion is anaemia, due in part to a decreased life span of mature erythrocytes. Recent studies have disclosed that cellular stress leads to an increase of cytosolic Ca2+ activity in erythrocytes thereby triggering cell shrinkage and breakdown of phosphatidylserine asymmetry of the cell membrane, both typical features of apoptosis. In the present experiments, phosphatidylserine exposure and cell size were measured by fluorescence-activated cell sorting (FACS) analysis of annexin binding and forward scatter, respectively. Erythrocytes from intact mice were compared with erythrocytes from mice exposed to a low-phosphate diet for 4 days. Annexin binding of freshly drawn erythrocytes was slightly but significantly enhanced by the low-phosphate diet. Furthermore, intracellular phosphate and ATP concentrations were significantly decreased in those erythrocytes whereas intracellular Ca2+ activity was unaltered. Osmotic shock (exposure to 700 mOsm by addition of sucrose for 12 h), removal of Cl- (replaced by gluconate for 15 h) or removal of glucose (12 h) decreased cell volume and increased the number of annexin-binding erythrocytes. Interestingly, these effects were significantly larger in erythrocytes from phosphate-depleted animals. The experiments reveal a novel mechanism triggered by phosphate depletion that presumably contributes to the enhanced vulnerability and accelerated sequestration of erythrocytes and, thus, to anaemia.