Efeito da hidroxiureia e progesterona na regulação da transcrição do gene da gama globina

AUTOR(ES)
DATA DE PUBLICAÇÃO

2002

RESUMO

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 tum, 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 patients. 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 as transcription factors), such as the GATA-I, 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 ofthe genetic expression ofthe transcription factors GATA-I, GATA-2 , NF-E2 and the gamma globin gene in erythroid lineage cells obtained iTomtwo-phase culture of peripheral blood donors at the Hemocenter, UNICAMP. The expression 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 (PO.O5,Wilcoxon test)

ASSUNTO(S)

hemoglobina anemia falciforme progesterona

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