LOCALIZATION OF SPECIFIC ERYTHROPOIETIN BINDING-SITES IN DEFINED AREAS OF THE MOUSE-BRAIN
LOCALIZATION OF SPECIFIC ERYTHROPOIETIN BINDING-SITES IN DEFINED AREAS OF THE MOUSE-BRAIN
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DOI：
10.1073/pnas.92.9.3717
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发表时间：
1995-04-25
影响因子：
11.1
通讯作者：
GASSMANN, M
中科院分区：
文献类型：
--
作者：
DIGICAYLIOGLU, M;BICHET, S;GASSMANN, M
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），其主要在成年哺乳动物的肾脏中产生并响应于缺氧而被诱导。EPO与细胞因子受体超家族成员EPO受体（EPO-R）的结合控制红细胞的终末成熟。然而，我们通过逆转录-PCR在小鼠大脑中检测到编码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程序）导致小鼠大脑中EPO mRNA增加20倍（通过竞争性逆转录PCR定量），而EPO-R mRNA水平不受缺氧影响，小鼠脑切片的结合研究显示，放射性碘标记的EPO在不同的脑区有明确的结合位点，EPO结合的特异性通过与过量未标记的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EPO与EPO-R的结合，另一种非抑制EPO与EPO-R的结合）来评估。在海马中观察到主要EPO结合位点，内囊、皮质和中脑区域。EPO-R的功能性表达和EPO的缺氧上调表明EPO在脑中的作用。
The main physiological regulator of erythropoiesis is the hematopoietic growth factor erythropoietin (EPO), which is primarily produced in the kidney of adult mammals and 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 tells. 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.