ERYTHROPOIETIN RETARDS DNA BREAKDOWN AND PREVENTS PROGRAMMED DEATH IN ERYTHROID PROGENITOR CELLS

ERYTHROPOIETIN RETARDS DNA BREAKDOWN AND PREVENTS PROGRAMMED DEATH IN ERYTHROID PROGENITOR CELLS
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DOI:
10.1126/science.2326648
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发表时间:
1990-04-20
期刊:
影响因子:
56.9
通讯作者:
BONDURANT, MC
BONDURANT, MC
中科院分区:
综合性期刊1区
文献类型:
--
作者:
KOURY, MJ;BONDURANT, MC

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促红细胞生成素控制哺乳动物红细胞产生的机制尚不清楚。体外[~3H]胸腺嘧啶核苷标记实验表明,红系祖细胞DNA断裂伴随着DNA修复和合成。促红细胞生成素使DNA裂解减少了2.6倍。在没有促红细胞生成素的情况下,红系祖细胞在2到4小时内积累DNA裂解片段,这是程序性细胞死亡(凋亡)中的特征,并在16小时后开始死亡。在促红细胞生成素存在的情况下,祖细胞存活并分化为网织红细胞。因此,细胞凋亡是正常红细胞生成的主要成分,而促红细胞生成素通过延缓DNA分解和阻止红系祖细胞的凋亡来控制红细胞的生成。
The mechanism by which erythropoietin controls mammalian erythrocyte production is unknown. Labeling experiments in vitro with [3H]thymidine demonstrated DNA cleavage in erythroid progenitor cells that was accompanied by DNA repair and synthesis. Erythropoietin reduced DNA cleavage by a factor of 2.6. In the absence of erythropoietin, erythroid progenitor cells accumulated DNA cleavage fragments characteristic of those found in programmed cell death (apoptosis) by 2 to 4 hours and began dying by 16 hours. In the presence of erythropoietin, the progenitor cells survived and differentiated into reticulocytes. Thus, apoptosis is a major component of normal erythropoiesis, and erythropoietin controls erythrocyte production by retarding DNA breakdown and preventing apoptosis in erythroid progenitor cells.