Investigating Disturbances of Oxygen Homeostasis: From Cellular Mechanisms to the Clinical Practice

Abstract

Soon after its discovery in the 18th century, oxygen was applied as a therapeutic agent to treat severely ill patients. Lack of oxygen, commonly termed as hypoxia, is frequently encountered in different disease states and is detrimental to human life. However, at the end of the 19th century, Paul Bert and James Lorrain Smith identified what is known as oxygen toxicity. The molecular basis of this phenomenon is oxygen’s readiness to accept electrons and to form different variants of aggressive radicals that interfere with normal cell functions. The human body has evolved to maintain oxygen homeostasis by different molecular systems that are either activated in the case of oxygen under-supply, or to scavenge and to transform oxygen radicals when excess amounts are encountered. Research has provided insights into cellular mechanisms of oxygen homeostasis and is still called upon in order to better understand related diseases. Oxygen therapy is one of the prime clinical interventions, as it is life saving, readily available, easy to apply and economically affordable. However, the current state of research also implicates a reconsidering of the liberal application of oxygen causing hyperoxia. Increasing evidence from preclinical and clinical studies suggest detrimental outcomes as a consequence of liberal oxygen therapy. In this review, we summarize concepts of cellular mechanisms regarding different forms of disturbed cellular oxygen homeostasis that may help to better define safe clinical application of oxygen therapy.

Effects of Hyperoxia on Mitochondrial Homeostasis: Are Mitochondria the Hub for Bronchopulmonary Dysplasia?

“…However, the molecular responses of living cells to altered gas conditions have been difficult to determine. Nevertheless, the continuous emergence of new techniques and technologies has facilitated more investigative options (Tretter et al, 2020). At the cellular level, 80 and 20% of available oxygen is utilized by mitochondria and other organelles, respectively.…”

Oxygen conditions oscillating between hypoxia and hyperoxia induce different effects in the pulmonary endothelium compared to constant oxygen conditions

“…In order to realistically model mechanical ventilation with different oxygen concentrations and patterns, it is also necessary to consider, that the mechanical force during this intervention imposes shear stress onto tissues, which can be aggravated by reorganization of the cytoskeleton due to oxidative stress as occurring under hyperoxia. According experimental systems are available, where cells are cultured in special chambers, where they can be stretched and simultaneously exposed to different gases at the same time (Tretter et al., 2020). It has been shown, that hyperoxia can induce polymerization of actin or, as in endothelial cells, an increase in actin stress fibers, thereby affecting cellular stiffness ((Roan et al., 2012) and references therein).…”

Anticancer therapeutic effect of cerium-based nanoparticles: known and unknown molecular mechanisms

“…73 Recent studies have demonstrated that ROS can be used to exploit the differences between the physiological environment and the TME, the latter of which exhibits abnormal characteristics, including acidosis, hypoxia, inflammation, overproduction of hydrogen peroxide, and vascular abnormalities. 74…”

“…73 Recent studies have demonstrated that ROS can be used to exploit the differences between the physiological environment and the TME, the latter of which exhibits abnormal characteristics, including acidosis, hypoxia, inflammation, overproduction of hydrogen peroxide, and vascular abnormalities. 74 A healthy intracellular ROS level contributes to the regulation of normal biological functions, including protein activation or inhibition, DNA mutagenesis, gene transcription activation, and antimicrobial action. 75 High levels of ROS, viz., oxidative stress, are linked to a variety of disorders, such as cancer, cardiovascular disease, neurological diseases, inflammatory diseases, and diabetes.…”