Maintenance of red blood cell integrity by AMP-activated protein kinase α1 catalytic subunit

Maintenance of red blood cell integrity by AMP-activated protein kinase α1 catalytic subunit
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DOI:
10.1016/j.febslet.2010.07.041
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发表时间:
2010-08-20
期刊:
影响因子:
3.5
通讯作者:
Viollet, Benoit
Viollet, Benoit
中科院分区:
生物学3区
文献类型:
--
作者:
Foretz, Marc;Guihard, Soizic;Viollet, Benoit

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AMP活化蛋白激酶(AMPK)在调节细胞能量代谢中起着关键作用。我们先前的研究表明,AMPKα1-/-小鼠出现中度贫血,并伴有脾肿大和高度网织红细胞增多。在这里,我们报告了AMPKα1-/-小鼠的脾切除加重了贫血,这支持了AMPKα1-/-小鼠通过脾内髓外红细胞生成而产生代偿反应的证据。将AMPKα1/-小鼠的骨髓移植到野生型受者体内,重现了血液学表型。此外,AMPKα1/-红细胞(RBC)对剪切力的响应表现出较小的变形能力,限制了它们的膜弹性。因此,我们的结果强调了AMPK在保持RBC完整性方面的关键作用。(C)2010年欧洲生化学会联合会。爱思唯尔出版,版权所有。
AMP-activated protein kinase (AMPK) plays a pivotal role in regulating cellular energy metabolism. We previously showed that AMPK alpha 1-/- mice develop moderate anemia associated with splenomegaly and high reticulocytosis. Here, we report that splenectomy of AMPK alpha 1-/- mice worsened anemia supporting evidence that AMPK alpha 1-/- mice developed a compensatory response through extramedullary erythropoiesis in the spleen. Transplantation of bone marrow from AMPK alpha 1-/- mice into wild-type recipients recapitulated the hematologic phenotype. Further, AMPK alpha 1-/- red blood cells (RBC) showed less deformability in response to shear stress limiting their membrane flexibility. Thus, our results highlight the crucial role of AMPK to preserve RBC integrity. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.