The hypoxia-inducible factor is stabilized in circulating hematopoletic stem cells under normoxic conditions
The hypoxia-inducible factor is stabilized in circulating hematopoletic stem cells under normoxic conditions
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DOI：
10.1016/j.febslet.2007.05.077
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发表时间：
2007-06-26
期刊：
影响因子：
3.5
通讯作者：
Capitanio, Nazzareno
中科院分区：
文献类型：
--
作者：
Piccoli, Claudia;D'Aprile, Annamaria;Capitanio, Nazzareno
缺氧诱导因子（HIF）转录系统使细胞适应有限的O-2可用性，将该信号转导成病理生理反应，如血管生成、红细胞生成、血管生成控制和改变的能量代谢，以及细胞存活决定。然而，已知除了缺氧之外的其他因素也能激活这种多效性转录因子。本研究的目的是描述人造血干细胞（HSC）中HIF的特征，并提供证据表明粒细胞集落刺激因子动员的CD 34（+）-和CD 133（+）-HSC表达稳定的HIF-1 α细胞质形式（在常氧条件下）。结果表明，HIF-1 α稳定与肿瘤抑制因子von Hippel-Lindau蛋白（pVHL）的下调相关，并受NADPH氧化酶依赖性活性氧产生的正向控制，表明动员的HSC中HIF的特异性O-2-独立转录后控制。这一新的发现进行了讨论的背景下提出的作用HIF作为一个调解人的祖细胞招聘受伤的缺血组织和/或在控制的未分化状态的维持。(c)2007年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
The hypoxia-inducible factor (HIF) transcriptional system enables cell adaptation to limited O-2 availability, transducing this signal into patho-physiological responses such as angiogenesis, erythropoiesis, vasomotor control, and altered energy metabolism, as well as cell survival decisions. However, other factors beyond hypoxia are known to activate this pleiotropic transcription factor. The aim of this study was to characterize HIF in human hematopoietic stem cells (HSCs) and evidence is provided that granulocyte colony stimulating factor-mobilized CD34(+)- and CD133(+)-HSCs express a stabilized cytoplasmic form of HIF-1 alpha( under normoxic conditions. It is shown that HIF-1 alpha stabilization correlates with down-regulation of the tumour suppressor von Hippel-Lindau protein (pVHL) and is positively controlled by NADPH-oxidase-dependent production of reactive oxygen species, indicating a specific O-2-independent post-transcriptional control of HIF in mobilized HSCs. This novel finding is discussed in the context of the proposed role of HIF as a mediator of progenitor cell recruitment to injured ischemic tissues and/or in the control of the maintenance of the undifferentiated state. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.