Mitoxantrone-Induced Suicidal Erythrocyte Death
Mitoxantrone-Induced Suicidal Erythrocyte Death
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DOI：
10.1159/000366376
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发表时间：
2014-01-01
影响因子：
--
通讯作者：
Lang, Florian
中科院分区：
文献类型：
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作者：
Arnold, Markus;Bissinger, Rosi;Lang, Florian
背景/目标：米托蒽醌是一种用于治疗恶性肿瘤和多发性硬化症的细胞毒性药物，至少部分通过触发细胞凋亡而有效。与有核细胞的凋亡类似，红细胞可能进入红细胞凋亡，一种自杀性细胞死亡。红细胞凋亡的特征是细胞皱缩和细胞膜混乱，磷脂酰丝氨酸移位到红细胞表面。红细胞凋亡的信号通路包括钙离子进入、神经酰胺形成和氧化应激。研究方法：细胞体积通过前向散射、膜联蛋白V结合的磷脂酰丝氨酸暴露、2 '，7'-二氯二氢荧光素-二乙酸荧光的反应性氧化剂物质（ROS）的形成和流式细胞术中荧光抗体结合的神经酰胺丰度来估计。结果如下：暴露于米托蒽醌48小时后，前向散射显著降低（>= 5 μ g/ml米托蒽醌），膜联蛋白-V结合增加（>= 10 μ g/ml米托蒽醌），ROS形成（25 μ g/ml米托蒽醌）和神经酰胺丰度（25 μ g/ml米托蒽醌）显著增加。米托蒽醌的效果没有显着修改的名义上没有细胞外钙离子，但显着钝化的抗氧化剂N-乙酰半胱氨酸（1 mM）。结论：米托蒽醌触发细胞膜扰乱，这种作用不需要细胞外Ca 2+的进入，但至少部分是由于ROS和神经酰胺的形成。版权所有（C）2014 S. Karger AG，巴塞尔
Background/Aims: Mitoxantrone, a cytotoxic drug used for the treatment of malignancy and multiple sclerosis, is at least in part effective by triggering apoptosis. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, a type of suicidal cell death. Hallmarks of eryptosis are cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signalling involved in eryptosis include Ca2+-entry, ceramide formation and oxidative stress. Methods: Cell volume was estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, formation of reactive oxidant species (ROS) from 2',7'-dichlorodihydrofluorescein-diacetate fluorescence, and ceramide abundance from binding of fluorescent antibodies in flow cytometry. Results: A 48 hours exposure to mitoxantrone was followed by significant decrease of forward scatter (>= 5 mu g/ml mitoxantrone) and increase of annexin-V-binding (>= 10 mu g/ml mitoxantrone), effects paralleled by significant increases of ROS formation (25 mu g/ml mitoxantrone) and ceramide abundance (25 mu g/ml mitoxantrone). The effect of mitoxantrone was not significantly modified by nominal absence of extracellular Ca2+ but significantly blunted by the antioxidant N-acetylcysteine (1 mM). Conclusions: Mitoxantrone triggers cell membrane scrambling, an effect not requiring entry of extracellular Ca2+ but at least partially due to formation of ROS and ceramide. Copyright (C) 2014 S. Karger AG, Basel