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Hydroxyurea-induced expression of glutathione peroxidase 1 in red blood cells of individuals with sickle cell anemia

Title
Hydroxyurea-induced expression of glutathione peroxidase 1 in red blood cells of individuals with sickle cell anemia
Authors
Cho C.-S.Kato G.J.Yang S.H.Bae S.W.Lee J.S.Gladwin M.T.Rhee S.G.
Ewha Authors
이서구배성원
SCOPUS Author ID
이서구scopusscopus
Issue Date
2010
Journal Title
Antioxidants and Redox Signaling
ISSN
1523-0864JCR Link
Citation
vol. 13, no. 1, pp. 1 - 11
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © Copyright 2010, Mary Ann Liebert, Inc.
DOI
10.1089/ars.2009.2978
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일반대학원 > 생명·약학부 > Journal papers
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