Transferrin receptor 2 mediates uptake of transferrin-bound and non-transferrin-bound iron
Transferrin receptor 2 mediates uptake of transferrin-bound and non-transferrin-bound iron
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DOI：
10.1016/j.jhep.2007.10.009
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发表时间：
2008-02-01
影响因子：
25.7
通讯作者：
Trinder, Debbie
中科院分区：
文献类型：
--
作者：
Graham, Ross M.;Reutens, Gail M.;Trinder, Debbie
背景/目的：转铁蛋白受体2似乎在铁代谢中具有双重作用;一个是信号传导，另一个是铁转运。它对高水平的二铁转铁蛋白敏感，这与铁过载的疾病有关。这些疾病中还存在血浆非转铁蛋白结合铁水平升高。本研究旨在阐明转铁蛋白受体2在转铁蛋白结合铁和非转铁蛋白结合铁摄入中的作用。方法：将转铁蛋白受体2转染的变异中国仓鼠卵巢（CHO）细胞与放射性标记的转铁蛋白结合铁或非转铁蛋白结合铁一起孵育。竞争的研究进行了未标记的双金属转铁蛋白的存在下，敲低进行使用特定的siRNA。结果：细胞表达转铁蛋白受体2结合和内化转铁蛋白和转铁蛋白结合铁。转铁蛋白回收发生的平均循环时间为11-15分钟。有趣的是，转铁蛋白受体2的存在下也与非转铁蛋白结合铁的吸收，这是由未标记的转铁蛋白结合金属抑制。结论：转铁蛋白受体2通过受体介导的内吞作用介导转铁蛋白结合铁的摄取。它还参与CHO细胞中非转铁蛋白结合铁的摄取和二铁转铁蛋白对非转铁蛋白结合铁摄取的抑制。（D 2007欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Transferrin receptor 2 appears to have dual roles in iron metabolism; one is signalling, the other is iron transport. It is sensitive to high levels of diferric transferrin, which is associated with disorders of iron overload. Also present in these disorders are increased levels of plasma non-transferrin-bound iron. This study sought to clarify the role of transferrin receptor 2 in the uptake of transferrin-bound and non-transferrin-bound iron.Methods: Variant Chinese Hamster Ovary (CHO) cells, transfected with transferrin receptor 2, were incubated with radio-labelled transferrin-bound or non-transferrin-bound iron. Competition studies were performed in the presence of unlabelled dimetallic transferrin; knockdown was performed using specific siRNA.Results: Cells expressing transferrin receptor 2 bound and internalised transferrin and transferrin-bound iron. Transferrin recycling occurred with an average cycling time of 11-15 min. Interestingly, the presence of transferrin receptor 2 was also associated with uptake of non-transferrin-bound iron which was inhibited by unlabelled transferrin-bound metals. Knockdown reduced transferrin-bound and non-transferrin-bound iron uptake by approximately 60%.Conclusions: Transferrin receptor 2 mediates transferrin-bound iron uptake by receptor-mediated endocytosis. It is also involved in the uptake of non-transferrin-bound iron and the inhibition of non-transferrin-bound iron uptake by diferric transferrin in CHO cells. (D 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.