The hereditary hemochromatosis protein, HFE, lowers intracellular iron levels independently of transferrin receptor 1 in TRVb cells
The hereditary hemochromatosis protein, HFE, lowers intracellular iron levels independently of transferrin receptor 1 in TRVb cells
复制标题
DOI：
10.1182/blood-2004-03-1204
复制
发表时间：
2005-03-15
期刊：
影响因子：
20.3
通讯作者：
Enns, CA
中科院分区：
文献类型：
--
作者：
Carlson, H;Zhang, AS;Enns, CA
遗传性血色素沉着症（HH）是一种常染色体隐性遗传病，可导致实质铁积累。HH最常见的形式是由HH蛋白中的单个氨基酸取代HFE引起的，但HFE调节铁稳态的机制尚不清楚。在缺乏转铁蛋白（Tf）的情况下，HFE与转铁蛋白受体1 （TfRI）相互作用，两种蛋白共内化，体外研究表明HFE和Tf竞争TfR1的结合。利用转染了不同形式的HFE和TfR1的缺乏内源性转铁蛋白受体的细胞系（TRVb细胞），我们证明了即使在低浓度下，Tf也能有效地与HFE在活细胞上结合TfR1。用HFE转染TRVb细胞或衍生系TRVb1（稳定表达人TfR1）导致铁蛋白水平降低，铁离子摄取减少。这些数据表明，HFE可以独立于其与TfR1的相互作用调节细胞内铁的储存。早期研究发现，在HeLa细胞中，HFE表达降低tf介导的铁摄取；本研究表明，HFE可降低TRVb细胞中的非tf结合铁，并进一步证明HFE可能在不同的细胞类型中发挥不同的作用。(c) 2005年由美国血液学会出版
Hereditary hemochromatosis (HH) is an autosomal recessive disease that leads to parenchymal iron accumulation. The most common form of HH is caused by a single amino acid substitution in the HH protein, HFE, but the mechanism by which HFE regulates iron homeostasis is not known. In the absence of transferrin (Tf), HFE interacts with transferrin receptor 1 (TfRI) and the 2 proteins co-internalize, and in vitro studies have shown that HFE and Tf compete for TfR1 binding. Using a cell line lacking endogenous transferrin receptors (TRVb cells) transfected with different forms of HFE and TfR1, we demonstrate that even at low concentrations Tf competes effectively with HFE for binding to TfR1 on living cells. Transfection of TRVb cells or the derivative line TRVb1 (which stably expresses human TfR1) with HFE resulted in lower ferritin levels and decreased Fe2+ uptake. These data indicate that HFE can regulate intracellular iron storage independently of its interaction with TfR1. Earlier studies found that in HeLa cells, HFE expression lowers Tf-mediated iron uptake; here we show that HFE lowers non-Tf-bound iron in TRVb cells and add to a growing body of evidence that HFE may play different roles in different cell types. (c) 2005 by The American Society of Hematology