Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages
Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages
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DOI：
10.1182/blood-2003-04-1250
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发表时间：
2003-12-01
期刊：
影响因子：
20.3
通讯作者：
Wessling-Resnick, M
中科院分区：
文献类型：
--
作者：
Knutson, MD;Vafa, MR;Wessling-Resnick, M
在网状内皮巨噬细胞中的ferroportin 1（FPN 1）的表达支持这一假设，即铁输出蛋白参与衰老红细胞的铁再循环。为了深入了解FPN 1在巨噬细胞铁代谢中的作用，我们研究了铁状态和红细胞吞噬作用对J774巨噬细胞中FPN 1表达的影响。北方分析表明，FPN 1 mRNA水平随铁耗竭而降低，随铁负荷而升高。铁诱导的FPN 1 mRNA的诱导被放线菌素D阻断，这表明转录控制是负责这种效果。在红细胞吞噬作用后，FPN 1 mRNA水平也上调，4小时后增加8倍，16小时后恢复到基础水平。Western分析表明FPN 1蛋白水平相应增加，10小时后诱导最大。铁螯合抑制FPN 1的mRNA和蛋白诱导后，红细胞吞噬，表明FPN 1诱导红细胞来源的铁。红细胞吞噬作用后铁相关基因的比较北方分析显示FPN 1水平在3小时后增加16倍，血红素加氧酶-1（HO-1）在3小时后增加10倍，天然抗性巨噬细胞相关蛋白1（Nramp 1）水平在6小时后增加2倍，但二价金属离子转运蛋白1（DMT 1）水平没有变化。在红细胞吞噬作用后FPN 1表达的快速和强烈诱导表明FPN 1在铁再循环中起作用。(C)2003年，美国血液学会。
The expression of ferroportin1 (FPN1) in reticuloendothelial macrophages supports the hypothesis that this iron-export protein participates in iron recycling from senescent erythrocytes. To gain insight into FPN1's role in macrophage iron metabolism, we examined the effect of iron status and erythrophagocytosis on FPN1 expression in J774 macrophages. Northern analysis indicated that FPN1 mRNA levels decreased with iron depletion and increased on iron loading. The iron-induced induction of FPN1 mRNA was blocked by actinomycin D, suggesting that transcriptional control was responsible for this effect. After erythrophagocytosis, FPN1 mRNA levels were also upregulated, increasing 8-fold after 4 hours and returning to basal levels by 16 hours. Western analysis indicated corresponding increases in FPN1 protein levels, with maximal induction after 10 hours. Iron chelation suppressed FPN1 mRNA and protein induction after erythrophagocytosis, suggesting that FPN1 induction results from erythrocyte-derived iron. Comparative Northern analyses of iron-related genes after erythrophagocytosis revealed a 16-fold increase in FPN1 levels after 3 hours, a 10-fold increase in heme oxygenase-1 (HO-1) after 3 hours, a 2-fold increase in natural resistance macrophage-associated protein 1 (Nramp1) levels after 6 hours, but no change in divalent metal ion transporter 1 (DMT1) levels. The rapid and strong induction of FPN1 expression after erythrophagocytosis suggests that FPN1 plays a role in iron recycling. (C) 2003 by The American Society of Hematology.