Triggering of eryptosis, the suicidal erythrocyte death, by phenoxodiol
Triggering of eryptosis, the suicidal erythrocyte death, by phenoxodiol
复制标题
DOI：
10.1007/s00210-019-01681-8
复制
发表时间：
2019-10-01
影响因子：
3.6
通讯作者：
Lang, Florian
中科院分区：
文献类型：
--
作者：
Fink, Madeline;Bhuyan, Abdulla Al Mamun;Lang, Florian
苯氧二醇用于治疗恶性肿瘤。该物质通过触发自杀性肿瘤细胞死亡或凋亡而有效。至少在理论上，苯恶二醇可以类似地刺激自杀性红细胞死亡或红细胞凋亡。胞吞的特征是细胞收缩和细胞膜不对称性的破坏，磷脂酰丝氨酸移位到红细胞表面。细胞凋亡的信号传导包括细胞溶质Ca 2+活性（[Ca 2 +]（i））的增加、活性氧（ROS）的形成和细胞表面神经酰胺丰度的增加。本研究探讨了苯恶二醇是否诱导红细胞凋亡，以及它是否改变了Ca 2+内流、ROS和神经酰胺。使用流式细胞术，通过膜联蛋白V结合、来自前向散射的细胞体积、来自Fluo 3荧光的[Ca 2 +]（i）、来自DCFDA依赖性荧光的ROS和使用特异性抗体的神经酰胺丰度来定量细胞表面处的磷脂酰丝氨酸暴露。人红细胞暴露于苯氧二醇（100 μ g/ml [416 μ M]）48小时后，膜联蛋白V结合细胞的百分比显著增加，平均前向散射和Fluo 3荧光显著降低，神经酰胺丰度显著增加，但并未显著改变DCFDA荧光。phenoxodiol对膜联蛋白V结合的影响趋于减少细胞外Ca 2+，效果，但是，没有达到统计学意义。总之，苯氧二醇触发红细胞凋亡，神经酰胺丰度增加的影响。
Phenoxodiol is used for the treatment of malignancy. The substance is effective by triggering suicidal tumor cell death or apoptosis. At least in theory, phenoxodiol could similarly stimulate suicidal erythrocyte death or eryptosis. Eryptosis is characterized by cell shrinkage and breakdown of cell membrane asymmetry with phosphatidylserine translocation to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca2+ activity ([Ca2+](i)), formation of reactive oxygen species (ROS), and increase of ceramide abundance at the cell surface. The present study explored whether phenoxodiol induces eryptosis and whether it modifies Ca2+ entry, ROS, and ceramide. Using flow cytometry, phosphatidylserine exposure at the cell surface was quantified from annexin V binding, cell volume from forward scatter, [Ca2+](i) from Fluo3 fluorescence, ROS from DCFDA-dependent fluorescence, and ceramide abundance utilizing specific antibodies. A 48-h exposure of human erythrocytes to phenoxodiol (100 mu g/ml [416 mu M]) significantly increased the percentage of annexin V binding cells, significantly decreased average forward scatter and Fluo3 fluorescence and significantly increased ceramide abundance, but did not significantly modify DCFDA fluorescence. The effect of phenoxodiol on annexin V binding tended to decrease following removal of extracellular Ca2+, an effect, however, not reaching statistical significance. In conclusion, phenoxodiol triggers eryptosis, an effect paralleled by increase of ceramide abundance.