Abstract
The hypoxia-inducible factor (HIF) transcriptional system enables cell adaptation to limited O2 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 O2-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.
| Original language | English |
|---|---|
| Pages (from-to) | 3111-3119 |
| Number of pages | 9 |
| Journal | FEBS Letters |
| Volume | 581 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - Jun 26 2007 |
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Keywords
- Hematopoietic stem cells
- HIF
- NADPH oxidase
- pVHL
- Redox signalling
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
The hypoxia-inducible factor is stabilized in circulating hematopoietic stem cells under normoxic conditions. / Piccoli, Claudia; D'Aprile, Annamaria; Ripoli, Maria; Scrima, Rosella; Boffoli, Domenico; Tabilio, Antonio; Capitanio, Nazzareno.
In: FEBS Letters, Vol. 581, No. 16, 26.06.2007, p. 3111-3119.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The hypoxia-inducible factor is stabilized in circulating hematopoietic stem cells under normoxic conditions
AU - Piccoli, Claudia
AU - D'Aprile, Annamaria
AU - Ripoli, Maria
AU - Scrima, Rosella
AU - Boffoli, Domenico
AU - Tabilio, Antonio
AU - Capitanio, Nazzareno
PY - 2007/6/26
Y1 - 2007/6/26
N2 - The hypoxia-inducible factor (HIF) transcriptional system enables cell adaptation to limited O2 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 O2-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.
AB - The hypoxia-inducible factor (HIF) transcriptional system enables cell adaptation to limited O2 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 O2-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.
KW - Hematopoietic stem cells
KW - HIF
KW - NADPH oxidase
KW - pVHL
KW - Redox signalling
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UR - http://www.scopus.com/inward/citedby.url?scp=34250163925&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2007.05.077
DO - 10.1016/j.febslet.2007.05.077
M3 - Article
VL - 581
SP - 3111
EP - 3119
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 16
ER -