Abstract
Chronic redox imbalance in erythrocytes of individuals with sickle cell disease (SCD) contributes to oxidative stress and likely underlies common etiologies of hemolysis. We measured the amounts of six antioxidant enzymes—SOD1, catalase, glutathione peroxidase 1 (GPx1), as well as peroxiredoxins (Prxs) I, II, and VI—in red blood cells (RBCs) of SCD patients and control subjects. The amounts of SOD1 and Prx VI were reduced by about 17% and 20%, respectively, in SCD RBCs compared with control cells. The amounts of Prx II and GPx1 did not differ between SCD and normal RBCs. However, about 18% of Prx II was inactivated in SCD RBCs as a result of oxidation to sulfinic Prx II, whereas inactive Prx II was virtually undetectable in control cells. Furthermore, GPx1 activity was reduced by about 33% in SCD RBCs, and the loss of activity was correlated with hemolysis in SCD patients. RBCs from SCD patients taking hydroxyurea demonstrated 90% higher GPx1 activity than did those from untreated SCD patients, with no differences seen for the other catalytic antioxidants. Hydroxyurea induced GPx1 expression in multiple cultured cell lines in a manner dependent on both p53 and NO-cGMP signaling pathways. GPx1 expression represents a previously unrecognized potential benefit of hydroxyurea treatment in SCD patients. Antioxid. Redox Signal. 13, 1–11.
Get full access to this article
View all access options for this article.
References
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
