Daghman N A, McHale C M, Savage G M, Price S, Winter P C, Maxwell A P, Lappin T R
Department of Haematology, The Queen's University of Belfast, Northern Ireland, United Kingdom.
Mol Genet Metab. 1999 Jun;67(2):113-7. doi: 10.1006/mgme.1999.2851.
Erythropoietin (Epo), a glycoprotein hormone produced principally in the fetal kidney and in the adult liver in response to hypoxia, is the prime regulator of growth and differentiation in erythroid progenitor cells. The regulation of Epo gene expression is not fully understood, but two mechanisms have been proposed. One involves the participation of a heme protein capable of reversible oxygenation and the other depends on the intracellular concentration of reactive oxygen species (ROS), assumed to be a function of pO2. We have investigated the production of Epo in response to three stimuli, hypoxia, cobalt chloride, and the iron chelator desferrioxamine, in Hep3B cells. As expected, hypoxia caused a marked rise in Epo production. When the cells were exposed to the paired stimuli of hypoxia and cobalt no further increase was found. In contrast, chelation of iron under hypoxic conditions markedly enhanced Epo production, suggesting that the two stimuli act by separate pathways. The addition of carbon monoxide inhibited hypoxia-induced Epo production, independent of desferrioxamine concentration. Taken together these data support the concept that pO2 and ROS are sensed independently.
促红细胞生成素（Epo）是一种主要在胎儿肾脏和成年肝脏中因缺氧而产生的糖蛋白激素，是红系祖细胞生长和分化的主要调节因子。Epo基因表达的调控尚未完全明确，但已提出两种机制。一种涉及一种能够进行可逆氧合的血红素蛋白的参与，另一种则取决于活性氧（ROS）的细胞内浓度，假定其是pO2的函数。我们研究了Hep3B细胞对三种刺激（缺氧、氯化钴和铁螯合剂去铁胺）的反应中Epo的产生情况。正如预期的那样，缺氧导致Epo产生显著增加。当细胞暴露于缺氧和钴的配对刺激时，未发现进一步增加。相反，在缺氧条件下铁螯合显著增强了Epo的产生，表明这两种刺激通过不同途径起作用。一氧化碳的添加抑制了缺氧诱导的Epo产生，且与去铁胺浓度无关。综合这些数据支持pO2和ROS是独立感知的这一概念。
