Role of ceruloplasmin in cellular iron uptake
Role of ceruloplasmin in cellular iron uptake
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DOI：
10.1126/science.279.5351.714
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发表时间：
1998-01-30
期刊：
影响因子：
56.9
通讯作者：
Fox, PL
中科院分区：
文献类型：
--
作者：
Mukhopadhyay, CK;Attieh, ZK;Fox, PL
遗传性铜蓝蛋白（Cp）缺乏的个体在大多数组织中有深刻的铁积累，这表明Cp对细胞铁的正常释放很重要。在这里，与预期相反，Cp显示出增加HepG 2细胞的铁摄取，使对底物的表观亲和力增加三倍。与其在铁吸收中的作用一致，Cp合成受铁供应的调节，铁耗竭后增加了4 - 5倍。与其他转录后调控的铁控制器不同，Cp合成受转录调控。因此，缺铁细胞可以增加Cp的合成，以维持细胞内铁稳态，因此，缺陷将导致铁在组织中的全球积累。
Individuals with hereditary ceruloplasmin (Cp) deficiency have profound iron accumulation in most tissues, which suggests that Cp is important for normal release of cellular iron. Here, in contrast to expectations, Cp was shown to increase iron uptake by HepG2 cells, increasing the apparent affinity for the substrate by three times. Consistent with its role in iron uptake, Cp synthesis was regulated by iron supply and was increased four- to fivefold after iron depletion. Unlike other iron controllers that are posttranscriptionally regulated, Cp synthesis was transcriptionally regulated. Thus, iron-deficient cells could increase Cp synthesis to maintain intracellular iron homeostasis, so that defects would lead to global accumulation of iron in tissues.