Stimulation of suicidal erythrocyte death by amantadine
Stimulation of suicidal erythrocyte death by amantadine
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DOI：
10.1016/j.ejphar.2007.11.051
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发表时间：
2008-02-26
影响因子：
5
通讯作者：
Lang, Florian
中科院分区：
文献类型：
--
作者：
Foeller, Michael;Geiger, Corinna;Lang, Florian
金刚烷胺是一种治疗帕金森病和病毒感染的有效药物。金刚烷胺的副作用包括贫血，这可能限制其治疗用途。金刚烷酸所致贫血的病因尚不明确。至少在理论上，贫血的部分原因可能是红细胞自杀性死亡或红细胞淤血，这加速了循环红细胞的清除。细胞萎缩的特点是细胞收缩和细胞膜混乱导致磷脂酰丝氨酸暴露在细胞表面。红细胞膜混乱的触发因素包括由Ca2+渗透性阳离子通道激活引起的胞质Ca2+浓度（[Ca2+](i)）的增加。目前的研究已经进行了测试金刚烷胺的作用，对下垂。健康志愿者的红细胞暴露于金刚烷胺和膜联蛋白V结合（暴露磷脂酰丝氨酸暴露），前向散射（反映细胞体积）和氟依赖性荧光（反映[Ca2+](i)），流式细胞术测定。红细胞暴露于金刚烷胺（>= 0.2 μ g/ml）增加[Ca2+](i)并触发膜联蛋白V结合，增加前向散射。在没有细胞外Ca2+的情况下，对膜联蛋白V结合的影响几乎被消除。目前的观察揭示的机制可能有助于金刚烷胺诱导贫血。(C) 2008 Elsevier B.V.版权所有
Amantadine is an effective drug for treatment of both, Parkinson's disease and viral infections. Side effects of amantadine include anemia, which may limit its therapeutic use. The cause of amantatine induced anemia is ill defined. At least in theory, the anemia could partially result from suicidal erythrocyte death or eryptosis, which accelerates the clearance of circulating erythrocytes. Eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. Triggers of erythrocyte membrane scrambling include an increase of cytosolic Ca2+ concentration ([Ca2+](i)) resulting from activation of Ca2+-permeable cation channels. The present study has been performed to test for an effect of amantadine on eryptosis. Erythrocytes from healthy volunteers were exposed to amantadine and annexin V binding (disclosing phosphatidylserine exposure), forward scatter (reflecting cell volume), and Fluo3-dependent fluorescence (reflecting [Ca2+](i)) were determined by flow cytometry. Exposure of erythrocytes to amantadine (>= 0.2 mu g/ml) increased [Ca2+](i) and triggered annexin V binding, and increased forward scatter. The effect on annexin V binding was virtually abolished in the absence of extracellular Ca2+. The present observations disclose mechanisms presumably contributing to amantadine induced anemia. (C) 2008 Elsevier B.V. All rights reserved.