The hypoxia-inducible factor is stabilized in circulating hematopoietic stem cells under normoxic conditions

Claudia Piccoli, Annamaria D'Aprile, Maria Ripoli, Rosella Scrima, Domenico Boffoli, Antonio Tabilio, Nazzareno Capitanio

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)3111-3119
Number of pages9
JournalFEBS Letters
Volume581
Issue number16
DOIs
Publication statusPublished - Jun 26 2007

Keywords

  • Hematopoietic stem cells
  • HIF
  • NADPH oxidase
  • pVHL
  • Redox signalling

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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