Accumulation of γ-globin mRNA in human erythroid cells treated with angelicin
Accumulation of γ-globin mRNA in human erythroid cells treated with angelicin
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DOI：
10.1034/j.1600-0609.2003.00113.x
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发表时间：
2003-09-01
影响因子：
3.1
通讯作者：
Gambari, R
中科院分区：
文献类型：
--
作者：
Lampronti, I;Bianchi, N;Gambari, R
本研究的目的是确定当归素是否能够增加人类红系细胞中γ-珠蛋白基因的表达。Angelicin在结构上与peptides相关，peptides是一种众所周知的化学类别的光敏剂，用于治疗不同的皮肤疾病（即，牛皮癣和白癜风）。为了验证当归素的活性，我们采用了两个实验细胞系统，人白血病K562细胞系和从正常供体分离的人红系祖细胞的两相液体培养。我们的研究结果表明，当归素，与阿糖胞苷，光神霉素和顺铂相比，是一个强大的诱导人白血病K562细胞的红系分化和γ-珠蛋白mRNA的积累。此外，当正常人红系前体细胞培养中的当归素的存在下，增加γ-珠蛋白mRNA的积累和胎儿血红蛋白（HbF）的生产，甚至高于使用羟基脲，被检测到。这些结果可能具有实际意义，因为药理学介导的人γ-珠蛋白基因表达的调节，导致HbF诱导，被认为是血液学疾病（包括β-地中海贫血和镰状细胞性贫血）的潜在治疗方法。
The aim of the present study was to determine whether angelicin is able to increase the expression of gamma-globin genes in human erythroid cells. Angelicin is structurally related to psoralens, a well-known chemical class of photosensitizers used for their antiproliferative activity in treatment of different skin diseases (i.e., psoriasis and vitiligo). To verify the activity of angelicin, we employed two experimental cell systems, the human leukemic K562 cell line and the two-phase liquid culture of human erythroid progenitors isolated from normal donors. The results of our investigation suggest that angelicin, compared with cytosine arabinoside, mithramycin and cisplatin, is a powerful inducer of erythroid differentiation and gamma-globin mRNA accumulation of human leukemia K562 cells. In addition, when normal human erythroid precursors were cultured in the presence of angelicin, increases of gamma-globin mRNA accumulation and fetal hemoglobin (HbF) production, even higher than those obtained using hydroxyurea, were detected. These results could have practical relevance, as pharmacologically-mediated regulation of the expression of human gamma-globin genes, leading to HbF induction, is considered a potential therapeutic approach in hematological disorders, including beta-thalassemia and sickle cell anemia.