The effect of iron overload and chelation on erythroid differentiation
The effect of iron overload and chelation on erythroid differentiation
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DOI：
10.1007/s12185-011-0988-3
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发表时间：
2012-02-01
影响因子：
2.1
通讯作者：
Kurokawa, Mineo
中科院分区：
文献类型：
--
作者：
Taoka, Kazuki;Kumano, Keiki;Kurokawa, Mineo
我们研究了铁超载和螯合引起的造血功能障碍的机制，特别是成红细胞分化的抑制。小鼠c-kit（+）祖细胞或人CD 34（+）外周血造血祖细胞在体外用游离铁和/或铁螯合剂分化为红系细胞。在铁超载，形成红系爆发形成单位集落和分化成成熟的成红细胞显着抑制，这些影响被取消铁螯合与去铁胺（DFO）。此外，过量的铁负荷通过升高细胞内活性氧（ROS）促进未成熟成红细胞凋亡。有趣的是，DFO和有效的抗氧化剂都降低了细胞内ROS水平并抑制了细胞凋亡，从而恢复了向成熟成红细胞的分化。因此，细胞内活性氧可能是治疗铁超载的一个新的治疗靶点。
We investigated the mechanisms of hematopoietic disorders caused by iron overload and chelation, in particular, the inhibition of erythroblast differentiation. Murine c-kit(+) progenitor cells or human CD34(+) peripheral blood hematopoietic progenitors were differentiated in vitro to the erythroid lineage with free iron and/or an iron chelator. Under iron overload, formation of erythroid burst-forming unit colonies and differentiation to mature erythroblasts were significantly suppressed; these effects were canceled by iron chelation with deferoxamine (DFO). Moreover, excessive iron burden promoted apoptosis in immature erythroblasts by elevating intracellular reactive oxygen species (ROS). Interestingly, both DFO and a potent anti-oxidant agent reduced intracellular ROS levels and suppressed apoptosis, thus restoring differentiation to mature erythroblasts. Accordingly, intracellular ROS may represent a new therapeutic target in the treatment of iron overload.