Regulation of erythrocyte survival by AMP-activated protein kinase
Regulation of erythrocyte survival by AMP-activated protein kinase
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DOI：
10.1096/fj.08-121772
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发表时间：
2009-04-01
期刊：
影响因子：
4.8
通讯作者：
Lang, Florian
中科院分区：
文献类型：
--
作者：
Foeller, Michael;Sopjani, Mentor;Lang, Florian
AMP激活的蛋白激酶（AMPK）是一种能量敏感酶，通过刺激能量产生和限制能量利用来抵消能量消耗。能量耗尽时，红细胞发生自杀性死亡或红细胞凋亡，由胞质Ca 2+活性（[Ca 2 +]（i））增加触发，特征为红细胞表面的细胞收缩和磷脂酰丝氨酸（PS）暴露。本研究探讨AMPK是否参与了红细胞凋亡的调控。Western blotting和共聚焦显微镜显示AMPK在红细胞中表达。[Ca2+]（i）（Fluo 3荧光）、细胞体积（前向散射）和PS暴露（膜联蛋白V结合）通过荧光激活细胞分选（FACS）分析测定。葡萄糖去除增加[Ca 2 +]（i），减少细胞体积，并增加PS暴露。AMPK抑制剂化合物C（20 μ M）在葡萄糖充足的条件下没有显着改变红细胞凋亡，但显着增强了葡萄糖戒断的红细胞凋亡作用。通过Ca 2+离子载体离子霉素增加[Ca 2 +]（i）触发红细胞凋亡，AMPK激活剂5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷（AICAR; 1 mM）减弱了这种作用。与野生型同窝仔（ampk（+/+））的红细胞相比，AMPK α 1缺陷小鼠（ampk（-/-））的红细胞对能量消耗的红细胞凋亡效应明显更敏感。ampk（-/-）小鼠贫血，尽管过度网织红细胞增多，他们患有严重的脾肿大，再次指出增强红细胞周转。这些观察结果揭示了AMPK在循环红细胞存活中的关键作用。Foller，M.，Sopjani，M.，科卡，S.，顾，S.，Mahmud，H.，Wang，K.，Floride，E.，Schleicher，E.，Schulz，E.，Munzel，T.，Lang，F.腺苷酸活化蛋白激酶对红细胞存活的调节。FASEB J. 23，1072-1080（2009）
AMP-activated protein kinase (AMPK), an energy-sensing enzyme, counteracts energy depletion by stimulation of energy production and limitation of energy utilization. On energy depletion, erythrocytes undergo suicidal death or eryptosis, triggered by an increase in cytosolic Ca2+ activity ([Ca2+](i)) and characterized by cell shrinkage and phosphatidylserine (PS) exposure at the erythrocyte surface. The present study explored whether AMPK participates in the regulation of eryptosis. Western blotting and confocal microscopy disclosed AMPK expression in erythrocytes. [Ca2+](i) (Fluo3 fluorescence), cell volume (forward scatter), and PS exposure (annexin V binding) were determined by fluorescence-activated cell sorting (FACS) analysis. Glucose removal increased [Ca2+](i), decreased cell volume, and increased PS exposure. The AMPK-inhibitor compound C (20 mu M) did not significantly modify eryptosis under glucose-replete conditions but significantly augmented the eryptotic effect of glucose withdrawal. An increase in [Ca2+](i) by Ca2+ ionophore ionomycin triggered eryptosis, an effect blunted by the AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; 1 mM). As compared with erythrocytes from wild-type littermates (ampk(+/+)), erythrocytes from AMPK alpha 1-deficient mice (ampk(-/-)) were significantly more susceptible to the eryptotic effect of energy depletion. The ampk(-/-) mice were anemic despite excessive reticulocytosis, and they suffered from severe splenomegaly, again pointing to enhanced erythrocyte turnover. The observations disclose a critical role of AMPK in the survival of circulating erythrocytes.-Foller, M., Sopjani, M., Koka, S., Gu, S., Mahmud, H., Wang, K., Floride, E., Schleicher, E., Schulz, E., Munzel, T., Lang, F. Regulation of erythrocyte survival by AMP-activated protein kinase. FASEB J. 23, 1072-1080 (2009)