Abstract
Effective metabolism is highly dependent on a narrow therapeutic range of oxygen. Accordingly, low levels of oxygen, or hypoxia, are one of the most powerful inducers of gene expression, metabolic changes, and regenerative processes, including angiogenesis and stimulation of stem cell proliferation, migration, and differentiation. The sensing of decreased oxygen levels (hypoxia) or increased oxygen levels (hyperoxia), occurs through specialized chemoreceptor cells and metabolic changes at the cellular level, which regulate the response. Interestingly, fluctuations in the free oxygen concentration rather than the absolute level of oxygen can be interpreted at the cellular level as a lack of oxygen. Thus, repeated intermittent hyperoxia can induce many of the mediators and cellular mechanisms that are usually induced during hypoxia. This is called the hyperoxic-hypoxic paradox (HHP). This article reviews oxygen physiology, the main cellular processes triggered by hypoxia, and the cascade of events triggered by the HHP.
Highlights
Oxygen is the third-most abundant element in the universe, after hydrogen and helium, and it is the most dominant effector of most living creatures on earth
vascular endothelial growth factor (VEGF) production is induced by hypoxia-inducible factor (HIF)-1 and goes on to stimulate the cellular processes needed for both angiogenesis and arteriogenesis
Yan et al evaluated the effect of HBOT on SIRT1 in a model of focal cerebral ischemia induced by middle cerebral artery occlusion and on primary cultured cortical neurons subjected to oxygen-glucose deprivation injury [84,85]
Summary
Oxygen is the third-most abundant element in the universe, after hydrogen and helium, and it is the most dominant effector of most living creatures on earth. The ability to maintain oxygen homeostasis is essential for survival, and all mammalian physiological systems evolved to ensure the optimal level of oxygen supplied to all cells in each organism This has transpired through the evolution of a complex physiological infrastructure for oxygen delivery (the lungs), oxygen transport carriers (erythrocytes and plasma), oxygen transport pathways (vascular system), and the pump (heart). In addition to the dynamic respiratory and metabolic systems allowing increased oxygen delivery, as outlined above, it is necessary to have regulating mechanisms at the cellular level. These are essential for survival at extreme environmental conditions and pathological/disease states where systemic regulation is insufficient. Numerous reports have suggested that CYP metabolites contribute to the hypoxia response in the systemic microvasculature and endothelium, and may contribute to hypoxic pulmonary vasoconstriction [6,9,10]
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