Identification and Localization of Divalent Metal Transporter-1 (DMT-1) in Term Human Placenta

Georgieff, M.; Wobken, J. K.; Welle, J.; Burdo, Joseph; Connor, James R.

doi:10.1053/plac.2000.0566

Cited by 106 publications

(76 citation statements)

References 23 publications

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“…In contrast to EPO-R, TfR has been observed only in syncytiotrophoblast and in the proximal ends of cytotrophoblast columns in human placenta [20,27]. While TfR is labeled as a receptor, it mediates syncytiotrophoblast uptake of iron and hence should be classified as a nutrient transporter [27,28].…”

Section: Discussionmentioning

confidence: 99%

Effects of chronic hypoxia in vivo on the expression of human placental glucose transporters

2006

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Birth weight is reduced and the risk of preeclampsia is increased in human high altitude pregnancies. There has been little work to determine whether hypoxia acts directly to reduce fetal growth (e.g. reduced blood flow and oxygen delivery), or via changes in functional capacities such as nutrient transport. We therefore investigated the expression of a primary nutrient transporter, the GLUT1 glucose transporter and two in vitro markers of hypoxia (erythropoietin receptor, EPO-R, and transferrin receptor, TfR) in the syncytial microvillous (MVM) and basal membrane fractions (BMF) of 13 high (3100 m) and 12 low (1600 m) altitude placentas from normal term pregnancies. Birth weight was lower at 3100 m than at 1600 m despite similar gestational age, but none of the infants were clinically designated as fetal growth restriction. EPO-R, TfR and GLUT1 were examined by immunoblotting and maternal circulating erythropoietin and transferrin by ELISA. EPO-R was greater on the MVM (C75%) and BMF (C25%) at 3100 m. TfR was 32% lower on the MVM at 3100 m. GLUT1 was 40% lower in the BMF at 3100 m. Circulating EPO was greater at high altitude, while transferrin was similar, and neither correlated with their membrane receptors. BMF GLUT1 was positively correlated with birth weight at high, but not low altitude. In this in vivo model of chronic placental hypoxia, syncytial EPO-R increased as expected, while nutrient transporters decreased, opposite to what has been observed in vitro. Therefore, hypoxia acts to reduce fetal growth not simply by reducing oxygen delivery, but also by decreasing the density of nutrient transporters.

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Section: Discussionmentioning

confidence: 99%

Effects of chronic hypoxia in vivo on the expression of human placental glucose transporters

2006

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“…It appears that the ferro-stat that functions after birth to control accrual of dietary iron also functions during fetal life, with the placental trophoblast functioning in analogy to the duodenal mucosa. 12 Ferroportin is highly expressed and colocalizes with HFE in placental trophoblast cells. 13,14 Ferroportin expression increases with gestational age in parallel with the fetus' increasing demand for iron.…”

Section: Iron Homeostasismentioning

confidence: 99%

Fetal and infantile hemochromatosis

Whitington

2006

Hepatology

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“…DMT1 is most abundantly expressed in the duodenal epithelia. The expression of DMT1 in other cell types of nearly most of the organs has also been identified including erythrocytes, renal epithelial cells, cardiomyocytes and human placenta epithelia (Ferguson et al, 2001;Georgieff et al, 2000;Ke et al, 2003;Levy et al, 1999). In brain, DMT1 exists in neurons, cerebral capillary endothelial cells that constitute the blood-brain barrier (BBB) and the choroid plexus epithelial cells that comprise the blood-CSF barrier (BCB) (Burdo et al, 2001;Siddappa et al, 2003;Siddappa et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of DMT1 expression in choroidal epithelia of the blood–CSF barrier following manganese exposure in vitro

Wang

Zheng

2006

Brain Research

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Divalent metal transporter 1 (DMT1), whose mRNA possesses a stem-loop structure in 3′-untranslated region, has been identified in most organs and responsible for transport of various divalent metal ions. Previous work from this laboratory has shown that manganese (Mn) exposure alters the function of iron regulatory protein (IRP) and increases iron (Fe) concentrations in the cerebrospinal fluid (CSF). This study was designed to test the hypothesis that Mn treatment, by acting on protein-mRNA binding between IRP and DMT1 mRNA, altered the expression of DMT1 in an immortalized choroidal epithelial Z310 cell line which was derived from rat choroid plexus epithelia, leading to a compartmental shift of Fe from the blood to the CSF. Immunocytochemistry confirmed the presence of DMT1 in Z310 cell. Following in vitro exposure to Mn at 100 μM for 24 and 48 h, the expression of DMT1 mRNA in Z310 cells was significantly increased by 45.4% (P < 0.05) and 78.1% (P < 0.01), respectively, as compared to controls. Accordingly, Western blot analysis revealed a significant increase of DMT1 protein concentrations at 48 h after Mn exposure (100 μM). Electrophoretic mobility shift assay (EMSA) showed that Mn exposure increased binding of IRP to DMT1 mRNA in cultured choroidal Z310 cells. Moreover, real-time RT-PCR revealed no changes in DMT1 heterogeneous nuclear RNA (hnRNA) levels following Mn exposure. These data suggest that Mn appears to stabilize the binding of IRP to DMT1 mRNA, thereby increasing the expression of DMT1. The facilitated transport of Fe by DMT1 at the blood-CSF barrier may partly contribute to Mn-induced neurodegenerative Parkinsonism.

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Identification and Localization of Divalent Metal Transporter-1 (DMT-1) in Term Human Placenta

Cited by 106 publications

References 23 publications

Effects of chronic hypoxia in vivo on the expression of human placental glucose transporters

Effects of chronic hypoxia in vivo on the expression of human placental glucose transporters

Fetal and infantile hemochromatosis

Upregulation of DMT1 expression in choroidal epithelia of the blood–CSF barrier following manganese exposure in vitro

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