G6PD is indispensable for erythropoiesis after the embryonic-adult hemoglobin switch

G6PD is indispensable for erythropoiesis after the embryonic-adult hemoglobin switch
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DOI:
10.1182/blood-2004-03-0835
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发表时间:
2004-11-15
期刊:
影响因子:
20.3
通讯作者:
Filosa, S
Filosa, S
中科院分区:
医学1区
文献类型:
--
作者:
Paglialunga, F;Fico, A;Filosa, S

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葡萄糖 6-磷酸脱氢酶 (G6PD) (EC 1.1.1.42) 是快速产生 NADPH 的必需酶,这是暴露于氧化应激时所需的。小鼠胚胎干(ES)细胞可以产生所有胚胎和胎儿/成人细胞类型。通过研究完全不能产生G6PD蛋白的G6pdDelta ES细胞产生的胚状体的体外分化,我们发现这些细胞能够分化为中胚层细胞、心肌细胞、肝细胞和原始红系细胞。然而,我们在此表明​​,发生血红蛋白转换后,确定的红细胞会因细胞凋亡而死亡。还原剂和半胱天冬酶抑制剂可以延迟这种细胞凋亡,但只有恢复 G6PD 活性才能阻止这种细胞凋亡。因此,G6PD 被证明对于确定的红细胞生成是不可或缺的。 (C) 2004 年,美国血液学会。
Glucose 6-phosphate dehydrogenase (G6PD) (EC 1.1.1.42) is an essential enzyme for the rapid production of NADPH, as required on exposure to oxidative stress. Mouse embryonic stem (ES) cells can produce all embryonic and fetal/adult cell types. By studying the in vitro differentiation of embryoid bodies produced from G6pdDelta ES cells that are totally unable to produce G6PD protein, we found that these cells are able to differentiate into mesodermal cells, cardiomyocytes, hepatocytes, and primitive erythroid cells. However, we show here that, after the hemoglobin switch has taken place, definitive erythrocytes die by apoptosis. This apoptotic death is delayed by reducing agents and by a caspase inhibitor, but it is prevented only by the restoration of G6PD activity. Thus, G6PD proves indispensable for definitive erythropoiesis. (C) 2004 by The American Society of Hematology.