Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro
Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro
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DOI：
10.1042/0264-6021:3560883
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发表时间：
2001-06-15
影响因子：
4.1
通讯作者：
McArdle, HJ
中科院分区：
文献类型：
--
作者：
Gambling, L;Danzeisen, R;McArdle, HJ
母亲在怀孕期间缺铁会导致发育中的胎儿贫血，但其严重程度往往比母亲轻。这种耐药性背后的机制尚未确定。我们测量了给予铁水平降低的饮食的妊娠大鼠胎盘中铁转移相关蛋白的表达，并研究了缺铁对跨BeWo细胞层铁转移的影响，BeWo细胞层是胎盘铁转移的模型。转铁蛋白受体在mRNA和蛋白水平均有表达增加。同样，铁反应元件(IRE)调控的二价金属转运蛋白1(DMT1)的表达也增加。相反，非IRE调节的异构体在mRNA水平上没有变化。DMT1蛋白水平显著升高。铁的外流被认为是由金属转运蛋白介导的。IREG1/Iron portin1/MTP1，并在与胎儿转铁蛋白结合之前将Fe(II)氧化成Fe(III)是由胎盘铜氧化酶进行的。缺铁对IREG1的表达无明显影响，但铜氧化酶活性升高。在用去铁胺(去铁胺)处理缺铁的BeWo细胞中，铁-转铁蛋白的铁积累增加，同时转铁蛋白受体的表达增加。同时，铁的外流也有所增加。显示出从根尖到基底外侧的较高的铁通量。数据显示，母亲缺铁时胎盘铁转运蛋白的表达上调，导致铁通量效率增加，从而使胎儿贫血的严重程度降低到最低。
Maternal iron deficiency during pregnancy induces anaemia in the developing fetus; however, the severity tends to be less than in the mother. The mechanism underlying this resistance has not been determined. We have measured placental expression of proteins involved in iron transfer in pregnant rats given diets with decreasing levels of iron and examined the effect of iron deficiency on iron transfer across BeWo cell layers, a model for placental iron transfer. Transferrin receptor expression was increased at both mRNA and protein levels. Similarly, expression of the iron-responsive element (IRE)-regulated form of the divalent metal transporter 1 (DMT1) was also increased. In contrast, the non-IRE regulated isoform showed no change in mRNA levels. Protein levels of DMT1 increased significantly. Iron efflux is thought to be mediated by the metal transporter protein. IREG1/ferroportin1/MTP1, and oxidation of Fe(II) to Fe(III) prior to incorporation into fetal transferrin is carried out by the placental copper oxidase. Expression of IREG1 was not altered by iron deficiency, whereas copper oxidase activity was increased. In BeWo cells made iron deficient by treatment with desferrioxamine ('deferioxamine'), iron accumulation from iron-transferrin increased, in parallel with increased expression of the transferrin receptor. At the same time, iron efflux also increased. showing a higher flux of iron from the apical to the basolateral side. The data show that expression of placental proteins of iron transport are up-regulated in maternal iron deficiency, resulting in an increased efficiency of iron flux and a consequent minimization of the severity of fetal anaemia.