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Type: Artigo de periódico
Title: Increased Soluble Guanylate Cyclase Activity In The Red Blood Cells Of Sickle Cell Patients.
Author: Conran, Nicola
Oresco-Santos, Camila
Acosta, Heloisa C
Fattori, André
Saad, Sara T O
Costa, Fernando F
Abstract: Activation of soluble guanylate cyclase (sGC) has been reported to up-regulate gamma-globin gene transcription in erythroid cell lines and primary erythroblasts. sGC is activated by nitric oxide (NO), subsequently catalysing the conversion of guanosine triphosphate to cyclic guanosine monophosphate (cGMP), which mediates various physiological responses. To study the importance of this mechanism in the erythroid cells of sickle cell patients, cGMP levels were measured in the red blood cells (RBC) of normal individuals, steady-state sickle cell patients (SS) and SS patients on hydroxyurea (HU) therapy (SS + HU). cGMP levels were found to be significantly higher in RBC of SS patients (SS RBC) than in RBC of normal individuals, and were further increased in RBC of SS + HU patients. cGMP levels correlated with fetal haemoglobin (HbF) levels in SS/SS + HU patients, but not with reticulocyte count. Furthermore, NO-stimulated sGC activity, following incubation of cells with a NO donor, was significantly greater in SS RBC than in normal RBC. These results demonstrate, for the first time, an increased metabolism of NO mediated by sGC in the SS RBC, which is further increased by hydroxyurea. Augmentation of cGMP levels by NO in erythroid cells may constitute a mechanism for induction of HbF and other erythrocyte functions and represent a possible therapeutic target for treatment of sickle cell disease.
Subject: Adult
Anemia, Sickle Cell
Antisickling Agents
Cyclic Gmp
Fetal Hemoglobin
Guanylate Cyclase
Middle Aged
Nitric Oxide Donors
Rna, Messenger
Reticulocyte Count
Citation: British Journal Of Haematology. v. 124, n. 4, p. 547-54, 2004-Feb.
Rights: fechado
Date Issue: 2004
Appears in Collections:Unicamp - Artigos e Outros Documentos

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