This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Scientists map the hidden protein network that helps red blood cells adapt to oxygen They account for nearly 83% of all cells in the human body, yet red blood cells are often portrayed as little more than bags of hemoglobin ferrying oxygen from the lungs to the heart and beyond. But new research from University of Colorado Anschutz reveals that they are vastly more complex, with far-reaching consequences for health, exercise and fitness.
In a study published today in Blood, scientists identified 3,775 proteins in ultra-pure mature human red blood cells—more than triple the estimates from just 15 years ago—and mapped thousands of physical interactions among them, revealing a surprisingly dynamic network that adapts quickly when oxygen levels fall. The findings offer new insight into how the body responds to low oxygen during high-altitude exposure and strenuous exercise, as well as during pathological hypoxia, including the severe loss of oxygen delivery that can occur after trauma and hemorrhagic shock. "Red blood cells are far more sophisticated than previously thought," said the study's senior author Angelo D'Alessandro, Ph.D., a professor of biochemistry and molecular genetics at CU Anschutz.
"They have no nucleus and cannot turn genes on or off to make new proteins. Yet every few seconds they move between oxygen-rich and oxygen-poor environments and have to adapt almost instantly. Our study shows that they accomplish this, in part, by continually reorganizing the proteins they already have." The center of this oxygen-sensitive network is Band 3, the most abundant protein in the red blood cell membrane.
The researchers discovered a previously unknown interaction between Band 3 and biliverdin reductase B, or BLVRB, connecting cell membrane changes to the metabolic machinery within it. When oxygen levels dropped, nearly one-third of the mapped protein interactions were remodeled. Binding between Band 3 and deoxygenated hemoglobin increased approximately threefold, while glucose metabolism shifted and production of 2,3-BPG increased.
This molecule reduces hemoglobin's grip on oxygen, helping red blood cells release oxygen to tissues that need it most. The findings may help explain how red blood cells adjust when people travel to or live at high altitude, where oxygen levels are lower. Red blood cells are known to increase 2,3-BPG during exposure to high altitude, helping compensate for reduced oxygen availability.
The new study identifies part of the molecular machinery that may coordinate that response. To test whether the mechanism mattered in a living organism, the researchers used animal models that lacked the oxygen-responsive N-terminal region of Band 3. Their red blood cells could no longer mount the normal metabolic response to low oxygen, and they showed impaired exercise capacity.
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