Increased soluble guanylate cyclase activity in the red blood cells of sickle cell patients

dc.creatorConran, N
dc.creatorOresco-Santos, C
dc.creatorAcosta, HC
dc.creatorFattori, A
dc.creatorSaad, STO
dc.creatorCosta, FF
dc.date2004
dc.dateFEB
dc.date2014-11-19T06:38:47Z
dc.date2015-11-26T17:58:16Z
dc.date2014-11-19T06:38:47Z
dc.date2015-11-26T17:58:16Z
dc.date.accessioned2018-03-29T00:41:50Z
dc.date.available2018-03-29T00:41:50Z
dc.identifierBritish Journal Of Haematology. Blackwell Publishing Ltd, v. 124, n. 4, n. 547, n. 554, 2004.
dc.identifier0007-1048
dc.identifierWOS:000188539200016
dc.identifier10.1111/j.1365-2141.2004.04810.x
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/60037
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/60037
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/60037
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1291693
dc.descriptionActivation 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.
dc.description124
dc.description4
dc.description547
dc.description554
dc.languageen
dc.publisherBlackwell Publishing Ltd
dc.publisherOxford
dc.publisherInglaterra
dc.relationBritish Journal Of Haematology
dc.relationBr. J. Haematol.
dc.rightsfechado
dc.sourceWeb of Science
dc.subjecterythrocytes
dc.subjecthydroxyurea
dc.subjectnitric oxide
dc.subjectsickle cell anaemia
dc.subjectsoluble guanylate cyclase
dc.subjectNitric-oxide
dc.subjectCyclic-gmp
dc.subjectIn-vitro
dc.subjectHydroxyurea
dc.subjectDisease
dc.subjectHemoglobin
dc.subjectExpression
dc.subjectQuantification
dc.subjectEndothelium
dc.subjectMechanism
dc.titleIncreased soluble guanylate cyclase activity in the red blood cells of sickle cell patients
dc.typeArtículos de revistas


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