Sickle cell disease (SCD) is characterized by abnormal hemoglobin, which alters the shape of red blood cells, resulting in poor blood flow and eventual death. In developed countries, the survival rate in children with SCD is high due to early medical intervention. However, the risk of adverse effects dramatically increases in SCD patients during early adulthood, and the factors that underlie adult progression of the disease are poorly understood. A new study in JCI Insight reports the results of a longitudinal study of SCD model mice that links impaired activity of the antioxidant regulator Nrf2 to intravascular red blood cell destruction and other adverse SCD-associated effects. Solomon Ofori-Acquah and colleagues at the University of Pittsburgh found that that the severity of hemolytic anemia, vascular inflammation, and lung injury increases with age in SCD mice. Pharmacological activation of Nrf2 in young animals improved survival and lessened age-related adverse effects. Additionally, expression of Nrf2 in non-blood cells was crucial for protection against tissue damage. Together, these results suggest that Nrf2 augmentation should be further explored for treating SCD.
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TITLE:
Non-hematopoietic Nrf2 dominantly impedes adult-progression of sickle cell anemia in mice
AUTHOR CONTACT:
Solomon Ofori-Acquah Sfo2@pitt.edu
View this article at: http://insight.jci.org/articles/view/81090?key=2a2c78edd80164456986
JCI Insight is the newest publication from the American Society of Clinical Investigation, a nonprofit honor organization of physician-scientists. JCI Insight is dedicated to publishing a range of translational biomedical research with an emphasis on rigorous experimental methods and data reporting. All articles published in JCI Insight are freely available at the time of publication. For more information about JCI Insight and all of the latest articles go to http://www.insight.jci.org.
Journal
JCI Insight