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Arsenic-induced suicidal erythrocyte death

机译:砷引起的自杀性红细胞死亡

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Environmental exposure to arsenic has been associated with anemia, which could result from suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and phosphatidylserine exposure at the erythrocyte surface. Eryptosis is triggered by increase in cytosolic Ca2+ concentration, ceramide and energy depletion. The present experiments explored, whether arsenic stimulates eryptosis. According to annexin V-binding, arsenic trioxide (7 μM) within 48 h significantly increased phosphatidylserine exposure of human erythrocytes without inducing hemolysis. According to forward scatter, arsenic trioxide (7 μM) significantly decreased cell volume. Moreover, Fluo3-fluorescence showed that arsenic (10 μM) significantly increased cytosolic Ca2+ concentration. According to binding of respective fluorescent antibodies, arsenic trioxide (10 μM) significantly increased ceramide formation. Arsenic (10 μM) further lowered the intracellular ATP concentration. Removal of extracellular Ca2+ or inhibition of the Ca2+-permeable cation channels with amiloride blunted the effects of arsenic on annexin V-binding and cell shrinkage. In conclusion, arsenic triggers suicidal erythrocyte death by increasing cytosolic Ca2+ concentration, by stimulating the formation of ceramide and by decreasing ATP availability.
机译:砷暴露于环境中与贫血有关,贫血可能由自杀性红细胞死亡或隐匿性导致,其特征是细胞收缩和红细胞表面磷脂酰丝氨酸暴露。胞浆中Ca 2 + 浓度,神经酰胺和能量消耗的增加触发了加密。本实验探讨了砷是否刺激隐匿性。根据膜联蛋白V结合,在48小时内三氧化二砷(7μM)显着增加了人类红细胞磷脂酰丝氨酸的暴露而没有引起溶血。根据前向散射,三氧化二砷(7μM)显着降低了细胞体积。此外,Fluo3-荧光显示砷(10μM)显着增加了胞质Ca 2 + 的浓度。根据各个荧光抗体的结合,三氧化二砷(10μM)显着增加了神经酰胺的形成。砷(10μM)进一步降低了细胞内ATP浓度。用阿米洛利清除细胞外Ca 2 + 或抑制Ca 2 + 渗透性阳离子通道,使砷对膜联蛋白V结合和细胞收缩的作用减弱。总之,砷通过增加胞浆中Ca 2 + 的浓度,刺激神经酰胺的形成以及降低ATP的利用率来触发自杀性红细胞死亡。

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