Stimulation of erythropoietin gene transcription during hypoxia and cobalt exposure.
Stimulation of erythropoietin gene transcription during hypoxia and cobalt exposure.
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DOI：
10.1182/blood.v73.1.13.13
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发表时间：
1989
期刊：
影响因子：
20.3
通讯作者：
S. Schuster;EV Badiavas;P. Costa-Giomi;R. Weinmann;A. Erslev;J. Caro
中科院分区：
文献类型：
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作者：
S. Schuster;EV Badiavas;P. Costa-Giomi;R. Weinmann;A. Erslev;J. Caro
促红细胞生成素是一种主要由肾脏产生的血浆糖蛋白，是红细胞祖细胞的生长和分化因子。肾促红细胞生成素的产生是通过mRNA水平的调节来响应组织氧合的变化。暴露于钴中，是促红细胞生成素产生的一种非生理性刺激，也通过诱导mRNA积累起作用。为了确定促红细胞生成素mRNA水平的变化是否源于促红细胞生成素基因转录的增强，我们使用离体大鼠肾细胞核进行了体外转录反应。在体外转录过程中标记的特异性核rna的定量显示，在贫血-缺氧和钴处理动物的肾核中，促红细胞生成素基因转录活跃，而在正常肾核中则检测不到促红细胞生成素转录活性。时间过程研究表明，转录刺激开始于钴处理后2至4小时，与mRNA和血浆促红细胞生成素积累的动力学相似。这些结果表明，组织缺氧和钴暴露特异性地增强促红细胞生成素基因的表达。促红细胞生成素产生的增加至少部分受到基因转录水平的调控。
Erythropoietin, a plasma glycoprotein produced primarily by the kidney, is a growth and differentiation factor for erythroid progenitor cells. Production of renal erythropoietin is regulated by modulation of mRNA levels in response to changes in tissue oxygenation. Exposure to cobalt, a nonphysiologic stimulus for erythropoietin production, also acts by inducing mRNA accumulation. To determine whether variations in erythropoietin mRNA levels result from enhanced transcription of the erythropoietin gene, in vitro transcription reactions were performed using isolated rat kidney cell nuclei. Quantitation of specific nuclear RNAs labeled during in vitro transcription revealed active erythropoietin gene transcription in kidney nuclei from anemic-hypoxic and cobalt-treated animals while erythropoietin transcriptional activity was undetectable in normal kidney nuclei. Time course studies showed that stimulation of transcription begins between two and four hours following cobalt treatment and parallels the kinetics of mRNA and plasma erythropoietin accumulation. These results indicate that tissue hypoxia and cobalt exposure specifically enhance erythropoietin gene expression. This increase in erythropoietin production is regulated at least in part at the level of gene transcription.