• Citer

Pulsed high oxygen induces a hypoxic-like response in Human Umbilical Endothelial Cells (HUVECs) and in humans.

par Cimino, Francesco;Balestra, Costantino ;Germonpré, Peter;De Bels, David ;Tillmans, Frauke;Saija, Antonina;Speciale, Antonio;Virgili, Fabio
Référence Journal of applied physiology (Bethesda, Md. : 1985)
Publication Publié, 2012-10

Article révisé par les pairs

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

It has been proposed that relative changes of oxygen availability rather than steady state hypoxic or hyperoxic conditions, play an important role in HIF transcriptional effects. According to this hypothesis describing the "normobaric oxygen paradox", normoxia following a hyperoxic event is sensed by tissues as an oxygen shortage, upregulating HIF-1 activity. With the aim of confirming at cellular and at functional level that normoxia following an hyperoxic event is "interpreted" as a hypoxic event, we report a combination of experiments addressing the effects of an intermittent increase of oxygen concentration on HIF-1 levels and the activity level of specific oxygen-modulated proteins in cultured human umbilical vein endothelial cells (HUVECs), and the effects hemoglobin (Hb) levels after intermittent breathing normobaric high (100%) and low (15%) oxygen in vivo in humans. Our experiments confirm that during recovery after hyperoxia, an increase of HIF expression occurs in HUVECs, associated to an increase of matrix metalloproteinases activity. These data suggest that endothelial cells "interpret" the return to normoxia after hyperoxia as a hypoxic stimulus. At functional level, our data show that both breathing 15% and 100% oxygen 30 minutes every other day for a period of 10 days, induces an increase of Hb levels in humans. This effect was enhanced after the cessation of the oxygen breathing. These results indicate that a sudden decrease in tissue oxygen tension after hyperoxia, may act as a trigger for EPO synthesis so corroborating the hypothesis that "relative" hypoxia is a potent stimulator of HIF mediated gene expressions.