Gambling L, Danzeisen R, Gair S, Lea R G, Charania Z, Solanky N, Joory K D, Srai S K, McArdle H J
The Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, Scotland, UK.
Biochem J. 2001 Jun 15;356(Pt 3):883-9. doi: 10.1042/0264-6021:3560883.
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.
孕期母体缺铁会导致发育中的胎儿贫血；然而，胎儿贫血的严重程度往往低于母亲。这种抵抗力的潜在机制尚未确定。我们测量了给予铁含量逐渐降低饮食的怀孕大鼠胎盘中铁转运相关蛋白的表达，并研究了缺铁对BeWo细胞层铁转运的影响，BeWo细胞层是胎盘铁转运的模型。转铁蛋白受体在mRNA和蛋白质水平均增加。同样，二价金属转运蛋白1（DMT1）的铁反应元件（IRE）调节形式的表达也增加。相比之下，非IRE调节的同工型在mRNA水平上没有变化。DMT1的蛋白质水平显著增加。铁外流被认为是由金属转运蛋白IREG1/铁转运蛋白1/MTP1介导的，在铁掺入胎儿转铁蛋白之前，Fe（II）氧化为Fe（III）是由胎盘铜氧化酶进行的。缺铁并未改变IREG1的表达，而铜氧化酶活性增加。在用去铁胺（“去铁敏”）处理使BeWo细胞缺铁的情况下，铁从转铁蛋白的积累增加，同时转铁蛋白受体的表达也增加。与此同时，铁外流也增加，表明从顶端到基底外侧的铁通量更高。数据表明，母体缺铁时胎盘铁转运蛋白的表达上调，导致铁通量效率提高，从而使胎儿贫血的严重程度降至最低。
