Changes in O2 availability have an important role in activating hypoxia inducible factor (HIF). Endothelial cells seem to “interpret” the return to normoxia after a hyperoxic as a hypoxic stimulus. Accordingly, an intermittent increase of oxygen concentration is associated with a parallel significantly increase of HIF-1 activity and of the level of specific oxygenmodulated proteins (e.g. matrix metalloproteinases) in HUVEC. At functional level, breathing both 15 and 100% oxygen 30 min every other day for a period of 10 days induces an increase of hemoglobin levels in vivo in humans. This effect is 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 erythropoietin synthesis, thus corroborating the hypothesis that “relative” hypoxia is a potent stimulator of HIF-mediated gene expressions. Several plant molecules have been reported to induce an para-hormetic response, by acting as ‘low-dose stressors’ able to set up cells to eventually oppose to more severe stresses inducing the activity of NRF-2 transcription factor. Also in this case, data obtained utilizing cultured cell model have been paired with observation taken from human subjects undergoing a standardized hyperoxic/hyperbaric stress by underwater diving, receiving a pre-dive polyphenol (anthocyanins) supplementation. Our results suggest the need to reconsider some hypothesis on the mechanisms of action of nutritional molecules on the endothelial functions modulated by oxygen availability, taking into account the complexity of ingested food and its metabolization. In summary: 1) Changes in O2 availability, rather than steady-state hypoxic or hyperoxic conditions, play an important role in hypoxia-inducible factor (HIF) transcriptional effects 2) the metabolic transformation of nutritional phytochemicals must be taken into account to understand the molecular basis of their activity

Pulsed high oxygen induces hypoxic-like responses in humans: the role of dietary phytochemicals and cellular adaptive response

SPECIALE, ANTONIO;CIMINO, Francesco
2014-01-01

Abstract

Changes in O2 availability have an important role in activating hypoxia inducible factor (HIF). Endothelial cells seem to “interpret” the return to normoxia after a hyperoxic as a hypoxic stimulus. Accordingly, an intermittent increase of oxygen concentration is associated with a parallel significantly increase of HIF-1 activity and of the level of specific oxygenmodulated proteins (e.g. matrix metalloproteinases) in HUVEC. At functional level, breathing both 15 and 100% oxygen 30 min every other day for a period of 10 days induces an increase of hemoglobin levels in vivo in humans. This effect is 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 erythropoietin synthesis, thus corroborating the hypothesis that “relative” hypoxia is a potent stimulator of HIF-mediated gene expressions. Several plant molecules have been reported to induce an para-hormetic response, by acting as ‘low-dose stressors’ able to set up cells to eventually oppose to more severe stresses inducing the activity of NRF-2 transcription factor. Also in this case, data obtained utilizing cultured cell model have been paired with observation taken from human subjects undergoing a standardized hyperoxic/hyperbaric stress by underwater diving, receiving a pre-dive polyphenol (anthocyanins) supplementation. Our results suggest the need to reconsider some hypothesis on the mechanisms of action of nutritional molecules on the endothelial functions modulated by oxygen availability, taking into account the complexity of ingested food and its metabolization. In summary: 1) Changes in O2 availability, rather than steady-state hypoxic or hyperoxic conditions, play an important role in hypoxia-inducible factor (HIF) transcriptional effects 2) the metabolic transformation of nutritional phytochemicals must be taken into account to understand the molecular basis of their activity
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3087632
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