It solely takes holding your breath for barely too lengthy to know that too little oxygen is dangerous for you. However are you able to even have an excessive amount of? Certainly, respiratory air with a better oxygen stage than your physique wants could cause well being issues and even dying.
However with scant analysis on the subject, scientists have identified little about how the physique senses an excessive amount of oxygen. Now, a brand new examine from Gladstone Institutes has expanded the scientific physique of data concerning the mechanisms at play and why it issues for well being.
Their findings, reported in Science Advances, clarify how respiratory air with completely different ranges of oxygen—from too little, to simply proper, or an excessive amount of—impacts the creation and degradation of various proteins within the lungs, coronary heart, and mind of mice. Notably, the examine additionally highlights a specific protein which will play a central position in regulating how cells reply to hyperoxia.
“These outcomes have implications for a lot of completely different ailments,” says Gladstone assistant investigator Isha Jain, PhD, senior writer of the brand new examine, in a launch. “Greater than 1 million individuals within the US breathe supplemental oxygen day-after-day for medical causes, and research recommend it may very well be making issues worse in some instances. That’s only one setting the place our work is beginning to clarify what’s occurring and the way the physique responds.”
Understanding Oxygen’s Results
Most prior analysis on oxygen ranges has examined the molecular results of too little oxygen. And even in that realm, many of the focus has been on how low oxygen impacts which genes are turned on or off.
“Our examine enters uncharted territory by utilizing mice and looking out downstream of gene expression at which proteins abnormally accumulate or degrade in response to completely different oxygen concentrations,” says Kirsten Xuewen Chen, first writer of the brand new paper and a graduate scholar at UC San Francisco, in a launch.
The analysis builds on the workforce’s prior work, which revealed that in response to an excessive amount of oxygen, sure proteins containing iron and sulfur clusters grow to be degraded, main cells to malfunction.
“Now, we wished to get a extra dynamic image of how proteins are regulated when oxygen ranges are too excessive or too low,” Chen says in a launch.
To take action, the workforce uncovered mice for a number of weeks to air with oxygen stage of 8%, 21% (the same old stage we breathe in Earth’s ambiance), or 60%. In the meantime, they gave the mice meals containing a definite type of nitrogen that the animals’ our bodies integrated into new proteins.
This nitrogen isotope acted as a “label” that enabled the researchers to calculate protein turnover charges—the stability between protein synthesis and degradation—for hundreds of various proteins within the lungs, coronary heart, and mind.
“We’re grateful to our collaborators who’re the consultants on this method, often called secure isotope labeling of amino acids in mice,” Jain says in a launch. “With out it, we couldn’t have completed this examine.”
A Key Protein Builds Up
The researchers discovered that oxygen ranges extra dramatically affected proteins within the lungs of mice than the center or mind. They recognized sure proteins with irregular turnover charges beneath high- or low-oxygen circumstances.
One explicit protein that amassed in high-oxygen circumstances, MYBBP1A, piqued their consideration. MYBBP1A is a transcription regulator, that means it instantly impacts gene expression.
“This caught our eye as a result of prior analysis has proven that different transcription elements known as hypoxia-inducible elements, or HIFs, play an enormous position in cells’ response to low oxygen,” Chen says in a launch. “Our work nominates MYBBP1A for a associated position in hyperoxia signaling.”
MYBBP1A is concerned within the manufacturing of ribosomes—mobile “machines” that construct proteins. Additional experiments surfaced clues that, in response to excessive oxygen ranges, accumulation of this protein within the lungs could have an effect on manufacturing of ribosomal RNA, a key part of ribosomes.
Jain’s workforce is now analyzing the exact molecular position of MYBBP1A throughout hyperoxia, together with whether or not its response is protecting or dangerous. This work might set the stage for novel remedies that concentrate on the MYBBP1A protein or related molecules in ways in which counter the dangerous results of hyperoxia—much like widespread analysis efforts focusing on HIF proteins in low-oxygen circumstances.
Researchers say the brand new examine presents a first-of-its variety dataset of protein turnover charges in several tissues of mice uncovered to completely different oxygen ranges. The workforce hopes its outcomes will encourage different researchers to additional examine the results of an excessive amount of or too little oxygen on the physique, which might rework the way in which we deal with illness.
Photograph caption: Gladstone assistant investigator Isha Jain, PhD, senior writer of the brand new examine, discusses the analysis with first writer Kirsten Xuewen Chen. Their findings clarify how respiratory air with completely different ranges of oxygen impacts the creation and degradation of various proteins within the lungs, coronary heart, and mind of mice.
Photograph credit score: Gladstone Institutes