Mild copper deficiency alters gene expression of proteins involved in iron metabolism
Mild copper deficiency alters gene expression of proteins involved in iron metabolism
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DOI：
10.1016/j.bcmd.2005.11.003
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发表时间：
2006-01-01
影响因子：
2.3
通讯作者：
Mazur, A
中科院分区：
文献类型：
--
作者：
Auclair, S;Feillet-Coudray, C;Mazur, A
铁和铜体内平衡共享共同的蛋白质，因此彼此紧密相连。例如，含铜蛋白质如血浆铜蓝蛋白和肝素蛋白在细胞输出过程中氧化Fe 2+，以在循环中与转铁蛋白结合运输。事实上，铜缺乏引起铁代谢紊乱，导致贫血和肝脏铁积累。本研究的目的是了解铜状态和铁代谢之间的相互作用。为此，我们建立了饮食铜缺乏症C57BL6雄性小鼠在12周。血液学参数，铜和铁的状态进行了评价。利用基因芯片技术研究了肝脏、十二指肠和脾脏中铁代谢相关蛋白的基因表达谱。我们的研究结果表明，铜缺乏导致小细胞和低色素性贫血以及肝脏铁超载。然而，基因表达谱表明，肝脏和肠道mRNA表达既不补偿肝脏铁过载，也不补偿在该小鼠模型中观察到的贫血。相反，基因表达的主要修改发生在脾脏。我们观察到转铁蛋白受体1和2以及血红素生物合成途径中涉及的几种蛋白质（亚铁螯合酶、UroD、UroS等）的mRNA水平增加。这些结果表明，铜缺乏小鼠响应于缺乏诱导的贫血的适应，导致红细胞合成的增加。(c)2005年爱思唯尔公司All rights reserved.
iron and copper homeostasis share common proteins and are therefore closely linked to each other. For example, copper-containing proteins like ceruloplasmin and hephaestin oxidize Fe2+ during cellular export processes for transport in the circulation bound to transferrin. Indeed, copper deficiency provokes iron metabolism disorders leading to anemia and liver iron accumulation.The aim of the present work was to understand the cross-talk between copper status and iron metabolism. For this purpose we have established dietary copper deficiency in C57BL6 male mice during twelve weeks. Hematological parameters, copper and iron status were evaluated. cDNA microarray studies were performed to investigate gene expression profiles of proteins involved in iron metabolism in the liver, duodenum and spleen. Our results showed that copper deficiency induces microcytic and hypochromic anemia as well as liver iron overload. Gene expression profiles, however, indicate that hepatic and intestinal mRNA expression neither compensates for hepatic iron overload nor the anemia observed in this mouse model. Instead, major modifications of gene expression occurred in the spleen. We observed increased mRNA levels of the transferrin receptors 1 and 2 and of several proteins involved in the heme biosynthesis pathway (ferrochelatase, UroD, UroS,...). These results suggest that copper-deficient mice respond to the deficiency induced anemia by an adaptation leading to an increase in erythrocyte synthesis. (c) 2005 Elsevier Inc. All rights reserved.