Bile Acid-Induced Suicidal Erythrocyte Death
Bile Acid-Induced Suicidal Erythrocyte Death
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DOI：
10.1159/000443091
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发表时间：
2016-01-01
影响因子：
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通讯作者：
Lang, Philipp A.
中科院分区：
文献类型：
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作者：
Lang, Elisabeth;Pozdeev, Vitaly I.;Lang, Philipp A.
背景/目的：在有核细胞中，胆汁酸可激活阳离子通道，随后导致Ca 2+进入。在红细胞中，胞质Ca 2+活性的增加触发红细胞凋亡，红细胞的自杀性死亡，其特征在于细胞表面的磷脂酰丝氨酸暴露和细胞皱缩。胆管结扎可引起胆汁淤积，这种作用部分归因于结合胆红素。本研究探讨了胆汁酸是否可以刺激眼睑下垂。研究方法：磷脂酰丝氨酸暴露的红细胞已被确定利用膜联蛋白V结合，细胞体积估计从前向散射，胞质Ca 2+活性测定使用Fluo-3荧光，和神经酰胺丰度在红细胞表面利用特异性抗体。结果如下：人红细胞暴露于甘氨鹅去氧胆酸（GCDC）和牛磺鹅去氧胆酸（TCDC）酸后，前向散射显著降低，Fluo-3荧光、神经酰胺丰度以及膜联蛋白V结合显著增加。对膜联蛋白V结合的影响显着减弱，但并没有通过去除细胞外Ca 2+而消除。结论：胆汁酸刺激自杀性细胞死亡，这一作用由Ca 2+内流和神经酰胺引起。胆汁酸诱导的红细胞增多可能反过来导致循环红细胞的加速清除，因此可能导致胆汁淤积患者的贫血。(C)2016作者（s）由S. Karger AG，巴塞尔
Background/Aims: In nucleated cells, bile acids may activate cation channels subsequently leading to entry of Ca2+. In erythrocytes, increase of cytosolic Ca2+ activity triggers eryptosis, the suicidal death of erythrocytes characterized by phosphatidylserine exposure at the cell surface and cell shrinkage. Eryptosis is triggered by bile duct ligation, an effect partially attributed to conjugated bilirubin. The present study explored, whether bile acids may stimulate eryptosis. Methods: Phosphatidylserine exposing erythrocytes have been identified utilizing annexin V binding, cell volume estimated from forward scatter, cytosolic Ca2+ activity determined using Fluo-3 fluorescence, and ceramide abundance at the erythrocyte surface utilizing specific antibodies. Results: The exposure of human erythrocytes to glycochenodesoxycholic (GCDC) and taurochenodesoxycholic (TCDC) acid was followed by a significant decrease of forward scatter and significant increase of Fluo-3 fluorescence, ceramide abundance as well as annexin V binding. The effect on annexin V binding was significantly blunted, but not abolished by removal of extracellular Ca2+. Conclusion: Bile acids stimulate suicidal cell death, an effect paralleled by and in part due to Ca2+ entry and ceramide. The bile acid induced eryptosis may in turn lead to accelerated clearance of circulating erythrocytes and, thus, may contribute to anemia in cholestatic patients. (C) 2016 The Author(s) Published by S. Karger AG, Basel