This study delves into the potential health risks associated with breathing air containing higher levels of oxygen than the body requires. While the detrimental effects of insufficient oxygen are well-known, there has been limited research on the consequences of excess oxygen. The Gladstone Institutes conducted a groundbreaking study to address this gap, significantly expanding our understanding of the mechanisms involved and their implications for health.
To investigate the impact of varying oxygen levels, the research team exposed mice to air with oxygen concentrations of 8 percent, 21 percent (typical atmospheric level), and 60 percent over several weeks. Concurrently, they introduced a unique form of nitrogen into the mice’s diet, acting as a label for tracking protein turnover rates— the balance between protein synthesis and degradation—across the lungs, heart, and brain.
The research findings, published in the journal Science Advances, provide insights into how the varying levels of oxygen inhaled, ranging from insufficient to optimal or excessive, influence the synthesis and breakdown of diverse proteins in the lungs, heart, and brain of mice. Significantly, the study brings attention to a specific protein that appears to have a crucial role in governing cellular responses to hyperoxia, the condition of elevated oxygen levels. “These results have implications for many different diseases,” states Gladstone Assistant Investigator Isha Jain, PhD, senior author of the new study. “More than 1 million people in the US breathe supplemental oxygen every day for medical reasons, and studies suggest it could be making things worse in some cases. That’s just one setting where our work is starting to explain what’s happening and how the body responds.”
The results revealed that oxygen levels had a more pronounced effect on proteins in the lungs compared to those in the heart or brain. Specific proteins exhibited abnormal turnover rates under both high and low oxygen conditions, with particular attention drawn to MYBBP1A, a transcription regulator influencing gene expression. Accumulation of MYBBP1A was noted in high-oxygen conditions, indicating a potential link between oxygen levels and gene regulation.
“We’re grateful to our collaborators who are the experts in this technique, known as stable isotope labeling of amino acids in mice,” Jain states. “Without it, we could not have done this study.”
A significant contribution of this study is the creation of a first-of-its-kind dataset detailing protein turnover rates in various tissues under different oxygen concentrations. The researchers hope that this dataset will serve as a valuable resource, inspiring further investigations into the effects of oxygen variations on the body. Ultimately, the findings hold the potential to revolutionize how we approach the treatment of diseases impacted by oxygen levels, prompting a new wave of research in this critical area of biology and medicine.
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