Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro

Lorraine Gambling, R Danzeisen, S Gair, R.g. Lea, Z Charania, N Solanky, K D Joory, S K Srai, Harry J McArdle

    Research output: Contribution to journalArticle

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    Abstract

    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.
    Original languageEnglish
    Pages (from-to)883-9
    Number of pages7
    JournalBiochemical Journal
    Volume356
    Issue numberPt 3
    Publication statusPublished - 15 Jun 2001

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    Carrier Proteins
    Iron
    Pregnancy Proteins
    In Vitro Techniques
    Transferrin Receptors
    Transferrin
    Anemia
    Proteins
    Mothers
    Fluxes
    Messenger RNA
    Deferoxamine
    Protein Transport
    Nutrition
    Rats
    Protein Isoforms
    Fetus
    Metals
    Cells

    Keywords

    • Anemia, Iron-Deficiency
    • Animals
    • Base Sequence
    • Carrier Proteins
    • Cation Transport Proteins
    • Cell Line
    • DNA Primers
    • Female
    • Iron
    • Iron-Binding Proteins
    • Membrane Proteins
    • Placenta
    • RNA, Messenger
    • Rats
    • Transferrin

    Cite this

    Gambling, L., Danzeisen, R., Gair, S., Lea, R. G., Charania, Z., Solanky, N., ... McArdle, H. J. (2001). Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro. Biochemical Journal, 356(Pt 3), 883-9.

    Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro. / Gambling, Lorraine; Danzeisen, R; Gair, S; Lea, R.g.; Charania, Z; Solanky, N; Joory, K D; Srai, S K; McArdle, Harry J.

    In: Biochemical Journal, Vol. 356, No. Pt 3, 15.06.2001, p. 883-9.

    Research output: Contribution to journalArticle

    Gambling, L, Danzeisen, R, Gair, S, Lea, RG, Charania, Z, Solanky, N, Joory, KD, Srai, SK & McArdle, HJ 2001, 'Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro', Biochemical Journal, vol. 356, no. Pt 3, pp. 883-9.
    Gambling L, Danzeisen R, Gair S, Lea RG, Charania Z, Solanky N et al. Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro. Biochemical Journal. 2001 Jun 15;356(Pt 3):883-9.
    Gambling, Lorraine ; Danzeisen, R ; Gair, S ; Lea, R.g. ; Charania, Z ; Solanky, N ; Joory, K D ; Srai, S K ; McArdle, Harry J. / Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro. In: Biochemical Journal. 2001 ; Vol. 356, No. Pt 3. pp. 883-9.
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    AU - Gambling, Lorraine

    AU - Danzeisen, R

    AU - Gair, S

    AU - Lea, R.g.

    AU - Charania, Z

    AU - Solanky, N

    AU - Joory, K D

    AU - Srai, S K

    AU - McArdle, Harry J

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    N2 - 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.

    AB - 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.

    KW - Anemia, Iron-Deficiency

    KW - Animals

    KW - Base Sequence

    KW - Carrier Proteins

    KW - Cation Transport Proteins

    KW - Cell Line

    KW - DNA Primers

    KW - Female

    KW - Iron

    KW - Iron-Binding Proteins

    KW - Membrane Proteins

    KW - Placenta

    KW - RNA, Messenger

    KW - Rats

    KW - Transferrin

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    VL - 356

    SP - 883

    EP - 889

    JO - Biochemical Journal

    JF - Biochemical Journal

    SN - 0264-6021

    IS - Pt 3

    ER -