The accumulation of high levels of oxidants in red blood cells dramatically decreases their lifespan and is associated with anemia.
Little was known about the molecular regulation of the response to oxidants in red blood cells, but in a study appearing in the August issue of the Journal of Clinical Investigation the protein FoxO3 is now shown to be required for mouse red blood cells to control their levels of oxidants and it is therefore probable that Foxo3 regulates the lifespan of these cells.
In the study, Saghi Ghaffari and colleagues from the Mount Sinai School of Medicine, New York, show that the induction of high levels of oxidants in mice lacking Foxo3 caused them to die rapidly.
Red blood cells from these mice expressed fewer proteins able to scavenge the oxidants and had a shorter lifespan than red blood cells from normal mice. Importantly, treatment of the cells with an antioxidant increased the lifespan of the red blood cells lacking Fox03.
A lack of Foxo3, and therefore high levels of oxidants, also decreased the rate of red blood cell development and led the authors to posit that it might be possible to exploit these functions of Fox03 to increase the lifespan and rate of development of red blood cells.
However, as Harvey Lodish, from the Whitehead Institute for Biomedical Research, notes in his accompanying commentary these data highlight "the importance of determining both the direct targets of Fox03 and its own regulation in helping us understand how a red blood cell lacking a nucleus knows exactly when to die."
Article: FoxO3 is required for the regulation of oxidative stress in erythropoiesis
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