Intermittent hypoxia changes HIF-1alpha phosphorylation pattern in endothelial cells: unravelling of a new PKA-dependent regulation of HIF-1alpha

Toffoli, Sébastien;Feron, Olivier;Raes, Martine;Michiels, Carine
(2007) Biochimica et Biophysica Acta : international journal of biochemistry and biophysics — Vol. 1773, n° 10, p. 1558-1571 (2007)

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Authors
  • Toffoli, Sébastien
    Author
  • Feron, Olivierorcid-logoUCLouvain
    Author
  • Raes, MartineUNamur
    Author
  • Michiels, Carine
    Author
Abstract
Vascularized tumors are exposed to intermittent hypoxia, that is, hypoxia followed by periods of reoxygenation. Abnormal structure and dysfunction of tumor blood vessels are responsible for these conditions. These repeated short periods of hypoxia concern tumor cells as well as endothelial cells. However, the effects of intermittent hypoxia are poorly understood. The aim of this study was to investigate the effects of intermittent hypoxia on endothelial cells and particularly on HIF-1alpha, a central actor in adaptive response to hypoxia. For that, endothelial cells were exposed to four repeated cycles of 1-h hypoxia followed by 30 min of reoxygenation. We showed that repeated cycles of hypoxia/reoxygenation induced a modification in HIF-l alpha phosphorylation pattern: a progressive increase in HIF-1alpha phosphorylated form was observed during the hypoxic periods. Activation of p42/p44, Akt and PKA was observed in parallel. PKA was shown to be involved in the phosphorylation of HIF-lalpha under intermittent hypoxia, while p42/p44 and Akt were not. As HIF-1 activity is often associated with enhanced cell survival, a better knowledge of the effects of intermittent hypoxia on endothelial cells and the highlight of particular mechanisms induced by intermittent hypoxia are essential to understand the behavior of endothelial cells during neo-angiogenesis.
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Toffoli, S., Feron, O., Raes, M., & Michiels, C. (2007). Intermittent hypoxia changes HIF-1alpha phosphorylation pattern in endothelial cells: unravelling of a new PKA-dependent regulation of HIF-1alpha. Biochimica et Biophysica Acta : international journal of biochemistry and biophysics, 1773(10), 1558-1571. https://doi.org/10.1016/j.bbamcr.2007.06.002 (Original work published 2007)