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The hypoxia‐inducible factor is stabilized in circulating hematopoietic stem cells under normoxic conditions
Author(s) -
Piccoli Claudia,
D'Aprile Annamaria,
Ripoli Maria,
Scrima Rosella,
Boffoli Domenico,
Tabilio Antonio,
Capitanio Nazzareno
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.05.077
Subject(s) - haematopoiesis , microbiology and biotechnology , erythropoiesis , transcription factor , stem cell , biology , hypoxia inducible factors , progenitor cell , hypoxia (environmental) , angiogenesis , cd34 , mediator , chemistry , cancer research , medicine , biochemistry , gene , organic chemistry , oxygen , anemia
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‐1α under normoxic conditions. It is shown that HIF‐1α 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.