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Dicoumarol Activates Ca2+-permeable Cation Channels Triggering Erythrocyte Cell Membrane Scrambling

机译:Dicoumarol激活Ca2 +渗透性阳离子通道,触发红细胞膜的争夺。

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Dicoumarol, a widely used anticoagulant, may cause anemia, which may result from enhanced erythrocyte loss due to bleeding or due to accelerated erythrocyte death. Erythrocytes may undergo suicidal death or eryptosis, characterized by cell shrinkage and phospholipid scrambling of the cell membrane. Eryptosis may be triggered by increase of cytosolic sup2+/sup-activity ([Casup2+/sup]subi/sub). The present study explored, whether dicoumarol induces eryptosis. [Casup2+/sup]subi/sub was estimated from Fluo3-fluorescence, cation channel activity utilizing whole cell patch clamp, cell volume from forward scatter, phospholipid scrambling from annexin-V-binding, and hemolysis from haemoglobin release. Exposure of erythrocytes for 48 hours to dicoumarol (=10 µM) significantly increased [Casup2+/sup]subi/sub, enhanced cation channel activity, decreased forward scatter, triggered annexin-V-binding and elicited hemolysis. Following exposure to 30 µM dicoumarol, annexin-V-binding affected approximately 15%, and hemolysis 2% of treated erythrocytes. The stimulation of annexin-V-binding by dicoumarol was abrogated in the nominal absence of sup2+/sup. In conclusion, dicoumarol stimulates suicidal death of erythrocytes by stimulating Casup2+/sup entry and subsequent triggering of sup2+/sup dependent cell membrane scrambling.
机译:广泛使用的抗凝剂双香豆酚可能引起贫血,这可能是由于出血或加速的红细胞死亡导致红细胞损失增加所致。红细胞可能会发生自杀性死亡或隐匿性死亡,其特征在于细胞收缩和细胞膜的磷脂扰乱。胞质 2 + -活性([Ca 2 + ] i )的增加可能触发了加密。本研究探讨了双香豆酚是否会诱导隐匿性。 [Ca 2 + ] i 由Fluo3-荧光估计,利用全细胞膜片钳的阳离子通道活性,正向散射的细胞体积,膜联蛋白-V-结合的磷脂扰乱以及血红蛋白释放引起的溶血。红细胞暴露于双香豆酚(= 10 µM)48小时显着增加[Ca 2 + ] i ,增强阳离子通道活性,降低前向散射,触发膜联蛋白-V-结合并引起溶血。暴露于30 µM的双香豆酚后,膜联蛋白V结合会影响约15%的红细胞和2%的溶血。在名义上不存在 2 + 的情况下,杜古香酚对膜联蛋白-V-结合的刺激作用被取消。总之,双香豆酚可通过刺激Ca 2 + 进入并随后触发 2 + 依赖性细胞膜扰动来刺激红细胞自杀死亡。

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