Induction of human fetal hemoglobin expression by adenosine-2',3'-dialdehyde.
Induction of human fetal hemoglobin expression by adenosine-2',3'-dialdehyde.
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DOI：
10.1186/1479-5876-11-14
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发表时间：
2013-01-14
影响因子：
7.4
通讯作者：
Zhao Q
中科院分区：
文献类型：
--
作者：
He Y;Rank G;Zhang M;Ju J;Liu R;Xu Z;Brown F;Cerruti L;Ma C;Tan R;Jane SM;Zhao Q
胎儿血红蛋白表达的药理学再激活是治疗镰状细胞病和β-地中海贫血的有前景的策略。本研究旨在探讨甲基转移酶抑制剂腺苷-2 '，3'-二醛（adenosine-2 '，3'-dialdehyde，Adenosine-2 '，Adenosine-2'，3 '-dialdehyde，Ad通过北方印迹分析和实时PCR评估人胎儿血红蛋白的表达水平。采用高效液相色谱法（HPLC）分析HbF和成人血红蛋白（HbA）含量。使用亚硫酸氢盐序列分析测定人γ-珠蛋白基因启动子上的DNA甲基化水平。通过染色体免疫沉淀（ChIP）评估基因上组蛋白标记的富集。在K562细胞和人骨髓红细胞系祖细胞中，阿托伐他汀通过可能涉及抑制蛋白质精氨酸甲基转移酶5（PRMT 5）的机制诱导γ-珠蛋白基因表达。甲基转移酶抑制剂（例如，Alcoxx）有效地重新激活胎儿血红蛋白表达的能力表明，这些药物可以提供重新激活胎儿珠蛋白表达的方法，作为治疗镰状细胞病和β-地中海贫血的治疗选择。
Pharmacologic reactivation of fetal hemoglobin expression is a promising strategy for treatment of sickle cell disease and β-thalassemia. The objective of this study was to investigate the effect of the methyl transferase inhibitor adenosine-2’,3’-dialdehyde (Adox) on induction of human fetal hemoglobin (HbF) in K562 cells and human hematopoietic progenitor cells. Expression levels of human fetal hemoglobin were assessed by northern blot analysis and Real-time PCR. HbF and adult hemoglobin (HbA) content were analyzed using high-performance liquid chromatography (HPLC). DNA methylation levels on human gamma-globin gene promoters were determined using Bisulfite sequence analysis. Enrichment of histone marks on genes was assessed by chromosome immunoprecipitation (ChIP). Adox induced γ-globin gene expression in both K562 cells and in human bone marrow erythroid progenitor cells through a mechanism potentially involving inhibition of protein arginine methyltransferase 5 (PRMT5). The ability of methyl transferase inhibitors such as Adox to efficiently reactivate fetal hemoglobin expression suggests that these agents may provide a means of reactivating fetal globin expression as a therapeutic option for treating sickle cell disease and β-thalassemia.
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影响因子：
64.8
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影响因子：
20.3
作者：
Fathallah, Hassana;Weinberg, Rona S.;Atweh, George F.
通讯作者：
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影响因子：
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作者：
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作者：
Hou, Zhaoyuan;Peng, Hongzhuang;Rauscher, Frank J., III
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