Artículos de revistas
Effect Of Hydroxyurea And Progester One In The Regulation Of The Expression Of The Beta-globin Gene [efeito Da Hidroxiuréia E Progesterona Na Regulação Da Transcrição Do Gene Da Gama Globin]
Registro en:
Revista Brasileira De Hematologia E Hemoterapia. , v. 24, n. 2, p. 147 - 148, 2002.
15168484
2-s2.0-52649128815
Autor
Duarte A.S.S.
Saad S.T.O.
Institución
Resumen
Sickle cell anemia is a very common hereditary disease caused by a structural defect in the beta-globin chain, giving rise to HbS. This anomalous hemoglobin, under low oxygen tensions, forms intracellular polymers, causing deformation of the erythrocytes which, in turn, block the micro-circulation and cause infarction in various organs. Pharmacological induction using various chemical compounds the best known being hydroxyurea (HU), 5-azacytidine, butyrate and steroid hormones, increase the synthesis of HbF in sickle cell patienta The regulation of the expression of HbF is related to the presence of active elements linked "cis" to the beta-globin as well as to the presence of regulatory proteins of the genomic transcription process (known astranscription factors), such as the GATA-1, GATA-2 and NF-E2 proteins expressed principally in the erythroid lineage This project aimed to study the effect of HU and the hormone progesterone on the modulation of the genetic expression of the transcription factors GATA-1, GATA-2, NF-E2 and the gamma globin genein erythroid lineage cells obtained from two-phase culture of peripheral blood donors at the Hemocenter, UNI CAMP. The express on of the transcription factors was determined by semi-quantitative RT-PCR and quantified by densitometry. Our results demonstrate that in the cells treated with HU and progesterone there was a significant increase, when compared with the untreated cells (p<0.05, Wilcoxon test), in the expression of the GATA-1 transcription factor and of the gamma globin gene after 96hs of phase II culture until termination at 216 hs. The expression of the NF-E2 transcription factor was not affected by HU or progester one administration during the entire process of erythroid differentiation and neither of the chemicals had any significant influence upon the expression of the GATA-2 transcription factor (p>O.O5, Wilcoxon test). 24 2 147 148