title: Hydroxyurea-induced expression of glutathione peroxidase 1 in red blood cells of individuals with sickle cell anemia.
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.
authors: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seodaemun-gu, Seoul, Korea.
authors: Chun-Seok
authors: CS
authors: Cho
authors: Gregory J
authors: GJ
authors: Kato
authors: Seung Ha
authors: SH
authors: Yang
authors: Sung Won
authors: SW
authors: Bae
authors: Jong Seo
authors: JS
authors: Lee
authors: Mark T
authors: MT
authors: Gladwin
authors: Sue Goo
authors: SG
authors: Rhee
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000201:enzymology; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology*; D005260:Female; D005979:Glutathione Peroxidase / Q000096:biosynthesis*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D008297:Male; D000094765:Glutathione Peroxidase GPX1
chemical_list: D005979:Glutathione Peroxidase; D006918:Hydroxyurea; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human