Mercury toxicokinetics of the healthy human term placenta involve amino acid transporters and ABC transporters

Elisabeth Straka, Isabella Ellinger, Christina Balthasar, Matthias Scheinast, Jasmin Schatz, Tamara Szattler, Sonja Bleichert, Leila Saleh, Martin Knöfler, Harald Zeisler, Markus Hengstschläger, Margit Rosner, Hans Salzer, Claudia Gundacker

Research output: Journal article (peer-reviewed)Journal article

39 Citations (Scopus)

Abstract

BACKGROUND: The capacity of the human placenta to handle exogenous stressors is poorly understood. The heavy metal mercury is well-known to pass the placenta and to affect brain development. An active transport across the placenta has been assumed. The underlying mechanisms however are virtually unknown.

OBJECTIVES: Uptake and efflux transporters (17 candidate proteins) assumed to play a key role in placental mercury transfer were examined for expression, localization and function in human primary trophoblast cells and the trophoblast-derived choriocarcinoma cell line BeWo.

METHODS: To prove involvement of the transporters, we used small interfering RNA (siRNA) and exposed cells to methylmercury (MeHg). Total mercury contents of cells were analyzed by Cold vapor-atomic fluorescence spectrometry (CV-AFS). Localization of the proteins in human term placenta sections was determined via immunofluorescence microscopy.

RESULTS: We found the amino acid transporter subunits L-type amino acid transporter (LAT)1 and rBAT (related to b(0,+) type amino acid transporter) as well as the efflux transporter multidrug resistance associated protein (MRP)1 to be involved in mercury kinetics of trophoblast cells (t-test P<0.05).

CONCLUSION: The amino acid transporters located at the apical side of the syncytiotrophoblast (STB) manage uptake of MeHg. Mercury conjugated to glutathione (GSH) is effluxed via MRP1 localized to the basal side of the STB. The findings can well explain why mercury is transported primarily towards the fetal side.

Original languageEnglish
Pages (from-to)34-42
Number of pages9
JournalToxicology
Volume340
DOIs
Publication statusPublished - 18 Jan 2016

Keywords

  • ATP-Binding Cassette Transporters/genetics
  • Amino Acid Transport System y+L
  • Amino Acid Transport Systems/genetics
  • Amino Acid Transport Systems, Basic/metabolism
  • Amino Acid Transport Systems, Neutral/metabolism
  • Biological Transport
  • Cell Line, Tumor
  • Choriocarcinoma/genetics
  • Female
  • Fusion Regulatory Protein 1, Light Chains/metabolism
  • Humans
  • Kinetics
  • Methylmercury Compounds/administration & dosage
  • Microscopy, Fluorescence
  • Multidrug Resistance-Associated Proteins/metabolism
  • Placenta/metabolism
  • Pregnancy
  • RNA Interference
  • Spectrometry, Fluorescence
  • Transfection
  • Trophoblasts/metabolism
  • Uterine Neoplasms/genetics
  • Term placenta
  • Primary trophoblast cells
  • Mercury toxicokinetics
  • Amino acid transporter
  • ABC transporter

ASJC Scopus subject areas

  • Toxicology

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