Stoichiometries of transferrin receptors 1 and 2 in human liver
Stoichiometries of transferrin receptors 1 and 2 in human liver
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DOI：
10.1016/j.bcmd.2009.09.004
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发表时间：
2010-01-15
影响因子：
2.3
通讯作者：
Enns, Caroline A.
中科院分区：
文献类型：
--
作者：
Chloupkova, Maja;Zhang, An-Sheng;Enns, Caroline A.
遗传性血色沉着症蛋白HFE或转铁蛋白受体2 TfR2的突变都会导致一种类似的严重形式的最常见的铁超负荷疾病，称为遗传性血色沉着症。HFE、TfR1和TfR2之间相互作用的模型表明，这些蛋白质在肝脏中以不同的摩尔浓度存在，它们控制铁调节激素海普西丁的表达，以响应体内铁负荷。本研究的目的是通过定量RT-PCR和定量免疫印迹法检测人肝组织中mRNA的活体水平和这些蛋白的浓度。TfR2基因的表达水平分别是TfR1和HFE的21倍和63倍。TfR2蛋白的摩尔浓度最高，在全细胞裂解产物中的摩尔浓度为1.95nmol/g蛋白，在微粒体膜中的摩尔浓度为10.89nmol/g蛋白。TfR1蛋白在全细胞裂解物和细胞膜中的摩尔浓度分别比TfR2低4.5倍和6.1倍。HFe蛋白含量低于0.53nmol/g总蛋白。因此，相对于TfR1和TfR2，HFe在人类肝组织中以亚化学计量浓度存在。这一发现支持一个模型，在该模型中，HFe的可用性限制了与TfR1或TfR2形成络合物的能力。(C)2009 Elsevier Inc.保留所有权利。
Mutations in either the hereditary hemochromatosis protein, HFE, or transferrin receptor 2, TfR2, result in a similarly severe form of the most common type of iron overload disease called hereditary hemochromatosis. Models of the interactions between HFE, TfR1, and TfR2 imply that these proteins are present in different molar concentrations in the liver, where they control expression of the iron regulatory hormone, hepcidin, in response to body iron loading. The aim of this study was to determine in vivo levels of mRNA by quantitative RT-PCR and concentrations of these proteins by quantitative immunoblotting in human liver tissues. The level of TfR2 mRNA was 21- and 63-fold higher than that of TfR1 and HFE, respectively. Molar concentration of TfR2 protein was the highest and determined to be 1.95 nmol/g protein in whole cell lysates and 10.89 nmol/g protein in microsomal membranes. Molar concentration of TfR1 protein was 4.5- and 6.1-fold lower than that of TfR2 in whole cell lysates and membranes, respectively. The level of HFE protein was below 0.53 nmol/g of total protein. HFE is thus present in substoichiometric concentrations with respect to both TfR1 and TfR2 in human liver tissue. This finding supports a model, in which availability of HFE is limiting for formation of complexes with TfR1 or TfR2. (C) 2009 Elsevier Inc. All rights reserved.