Fibach Eitan
Department of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
J Signal Transduct. 2011;2011:860985. doi: 10.1155/2011/860985. Epub 2011 Jul 14.
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 into hemoglobin (Hb)-containing RBCs. The activity of various protein tyrosine phosphatases, including those involved in the Epo pathway, can be inhibited by sodium orthovanadate (Na(3)VO(4), vanadate). Adding vanadate to cultured erythroid precursors of normal donors and patients with β-thalassemia enhanced cell proliferation and arrested maturation. This was associated with an increased production of fetal hemoglobin (HbF). Increased HbF in patients with β-hemoglobinopathies (β-thalassemia and sickle cell disease) ameliorates the clinical symptoms of the disease. These results raise the possibility that specific and nontoxic inhibitors of phosphatases may be considered as a therapeutic modality for elevating HbF in patients with β-hemoglobinopathies as well as for intensifying the Epo response in other forms of anemia.
红细胞生成是由促红细胞生成素（Epo）作用引发的，它通过与骨髓中红系前体细胞表面的受体（Epo-R）结合来实现。Epo信号的强度和持续时间受多种因素调节，包括激酶和磷酸酶活性之间的平衡。Epo信号决定了前体细胞增殖并成熟为含血红蛋白（Hb）的红细胞。多种蛋白酪氨酸磷酸酶的活性，包括那些参与Epo通路的磷酸酶，可被原钒酸钠（Na(3)VO(4)，钒酸盐）抑制。向正常供体及β地中海贫血患者的培养红系前体细胞中添加钒酸盐可增强细胞增殖并使成熟停滞。这与胎儿血红蛋白（HbF）产量增加相关。β血红蛋白病（β地中海贫血和镰状细胞病）患者体内HbF增加可改善疾病的临床症状。这些结果提示，磷酸酶的特异性无毒抑制剂有可能被视为一种治疗方式，用于提高β血红蛋白病患者的HbF水平，以及增强其他形式贫血中的Epo反应。
