Enhanced Fetal Hemoglobin Production by Phenylacetate and 4-Phenylbutyrate in Erythroid Precursors Derived From Normal Donors and Patients With Sickle Cell Anemia and P-Thalassemia
نویسندگان
چکیده
In both sickle cell (SS) anemia and @-thalassemia (,T-thal), an increase in fetal hemoglobin (HbF) ameliorates the clinical symptoms of the underlying disease. Several pharmacologic agents have been used to elevate HbF levels in adults; however. concerns regarding adverse effects of the prevailing drugs raise an urgent need for other agents capable of stimulating HbF production. We show here that sodium phenylacetate (NaPA) and its precursor, sodium 4phenylbutyrate (NaPB), can enhance HbF production in cultured erythroid progenitor derived from normal donors and patients with SS anemia or @-thal, when used at pharmacologic concentrations. Treatment resulted in (1 ) reduced cell proliferation, (2) elevated hemoglobin (Hb) content per cell (mean cellular Hb [MCH]), and (3) an increased proportion of HbF produced, associated with elevated lev-
منابع مشابه
Enhanced fetal hemoglobin production by phenylacetate and 4-phenylbutyrate in erythroid precursors derived from normal donors and patients with sickle cell anemia and beta-thalassemia.
In both sickle cell (SS) anemia and beta-thalassemia (beta-thal), an increase in fetal hemoglobin (HbF) ameliorates the clinical symptoms of the underlying disease. Several pharmacologic agents have been used to elevate HbF levels in adults; however, concerns regarding adverse effects of the prevailing drugs raise an urgent need for other agents capable of stimulating HbF production. We show he...
متن کاملInvolvement of Phosphatases in Proliferation, Maturation, and Hemoglobinization of Developing Erythroid Cells
Production of RBCs is triggered by the action of erythropoietin (Epo) through its binding to surface receptors (Epo-R) on erythroid precursors in the bone marrow. The intensity and the duration of the Epo signal are regulated by several factors, including the balance between the activities of kinesase and phosphatases. The Epo signal determines the proliferation and maturation of the precursors...
متن کاملResveratrol: Antioxidant activity and induction of fetal hemoglobin in erythroid cells from normal donors and β-thalassemia patients.
Thalassemia and sickle-cell anemia (SCA) present a major public health problem in countries where the number of carriers and affected individuals is high. As a result of the abnormalities in hemoglobin production, cells of thalassemia and SCA patients exhibit oxidative stress, which ultimately is responsible for the chronic anemia observed. Theref...
متن کاملSOX6 Downregulation Induces γ-Globin in Human β-Thalassemia Major Erythroid Cells
Background Fetal hemoglobin (HbF; α2γ2) is a potent genetic modifier of the severity of β-thalassemia and sickle cell anemia. Differences in the levels of HbF that persist into adulthood affect the severity of sickle cell disease and the β-thalassemia syndromes. Sry type HMG box (SOX6) is a potent silencer of HbF. Here, we reactivated γ-globin expression by downregulating SOX6 to alleviate anem...
متن کاملSide effects of hydroxyurea in patients with Thalassemia major and thalassemia intermedia and sickle cell anemia
Background Sickle hemoglobin is the most common abnormal hemoglobin in the United States. Hemoglobin S arises as a result of a single amino acid substitution (glutamic acid to valin at position 6 of the β-globine chain). The presence of fetal hemoglobin (HbF) plays a relatively protective role since a significant amount of HbF interferes with HbS polymerization, the pathogenesis mechanism of ...
متن کامل