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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Localization of specific erythropoietin binding sites in defined areas of the mouse brain.
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Localization of specific erythropoietin binding sites in defined areas of the mouse brain.

机译：特定促红细胞生成素结合位点在小鼠大脑定义区域的定位。

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摘要

The main physiological regulator of erythropoiesis is the hematopoietic growth factor erythropoietin (EPO), which is induced in response to hypoxia. Binding of EPO to the EPO receptor (EPO-R), a member of the cytokine receptor superfamily, controls the terminal maturation of red blood cells. So far, EPO has been reported to act mainly on erythroid precursor cells. However, we have detected mRNA encoding both EPO and EPO-R in mouse brain by reverse transcription-PCR. Exposure to 0.1% carbon monoxide, a procedure that causes functional anemia, resulted in a 20-fold increase of EPO mRNA in mouse brain as quantified by competitive reverse transcription-PCR, whereas the EPO-R mRNA level was not influenced by hypoxia. Binding studies on mouse brain sections revealed defined binding sites for radioiodinated EPO in distinct brain areas. The specificity of EPO binding was assessed by homologous competition with an excess of unlabeled EPO and by using two monoclonal antibodies against human EPO, one inhibitory and the other noninhibitory for binding of EPO to EPO-R. Major EPO binding sites were observed in the hippocampus, capsula interna, cortex, and midbrain areas. Functional expression of the EPO-R and hypoxic upregulation of EPO suggest a role of EPO in the brain.
机译：促红细胞生成的主要生理调节因子是造血生长因子促红细胞生成素（EPO），它是在对缺氧的反应中被诱导的。 EPO与EPO受体（EPO-R）（细胞因子受体超家族的成员）的结合控制着红细胞的终末成熟。到目前为止，据报道EPO主要作用于类红细胞前体细胞。但是，我们已经通过逆转录PCR检测到了编码小鼠脑中EPO和EPO-R的mRNA。暴露于0.1％一氧化碳（一种导致功能性贫血的过程）导致小鼠脑中EPO mRNA的增加20倍（通过竞争性逆转录PCR定量），而EPO-R mRNA水平不受缺氧的影响。对小鼠大脑切片的结合研究揭示了在不同大脑区域中放射性碘化EPO的定义结合位点。 EPO结合的特异性通过与过量的未标记EPO的同源竞争和通过使用两种抗人EPO的单克隆抗体，一种抑制性和另一种非抑制性的EPO与EPO-R的结合来评估。在海马，囊内膜，皮层和中脑区域观察到主要的EPO结合位点。 EPO-R的功能性表达和EPO的低氧上调表明EPO在大脑中的作用。

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