title: Mercury toxicokinetics of the healthy human term placenta involve amino acid transporters and ABC transporters.
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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Medical Genetics, Medical University Vienna, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Straka
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University Vienna, Vienna, Austria.
authors.forename: Isabella
authors.initials: I
authors.lastname: Ellinger
authors.affiliation: Institute of Medical Genetics, Medical University Vienna, Vienna, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Balthasar
authors.affiliation: Institute of Medical Genetics, Medical University Vienna, Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Scheinast
authors.affiliation: Institute of Medical Genetics, Medical University Vienna, Vienna, Austria.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Schatz
authors.affiliation: Institute of Medical Genetics, Medical University Vienna, Vienna, Austria.
authors.forename: Tamara
authors.initials: T
authors.lastname: Szattler
authors.affiliation: Institute of Medical Genetics, Medical University Vienna, Vienna, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Bleichert
authors.affiliation: Department of Obstetrics and Fetal-Maternal Medicine, Medical University Vienna, Vienna, Austria.
authors.forename: Leila
authors.initials: L
authors.lastname: Saleh
authors.affiliation: Department of Obstetrics and Fetal-Maternal Medicine, Medical University Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Knöfler
authors.affiliation: Department of Obstetrics and Fetal-Maternal Medicine, Medical University Vienna, Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Zeisler
authors.affiliation: Institute of Medical Genetics, Medical University Vienna, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Hengstschläger
authors.affiliation: Institute of Medical Genetics, Medical University Vienna, Vienna, Austria.
authors.forename: Margit
authors.initials: M
authors.lastname: Rosner
authors.affiliation: Clinic for Pediatrics and Adolescent Medicine, University Hospital Tulln, Tulln, Austria.
authors.forename: Hans
authors.initials: H
authors.lastname: Salzer
authors.affiliation: Institute of Medical Genetics, Medical University Vienna, Vienna, Austria. Electronic address: claudia.gundacker@meduniwien.ac.at.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gundacker
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D027241:Amino Acid Transport System y+L; D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism*; D026923:Amino Acid Transport Systems, Basic / Q000378:metabolism; D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism; D001692:Biological Transport; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism; D005260:Female; D027301:Fusion Regulatory Protein 1, Light Chains / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D034622:RNA Interference; D013050:Spectrometry, Fluorescence; D014162:Transfection; D014327:Trophoblasts / Q000378:metabolism; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D027241:Amino Acid Transport System y+L; D026905:Amino Acid Transport Systems; D026923:Amino Acid Transport Systems, Basic; D026921:Amino Acid Transport Systems, Neutral; D027301:Fusion Regulatory Protein 1, Light Chains; D008767:Methylmercury Compounds; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C489857:SLC3A1 protein, human; C421261:SLC7A7 protein, human; C421109:multidrug resistance-associated protein 1
keywords: ABC transporter; Amino acid transporter; Mercury toxicokinetics; Primary trophoblast cells; Term placenta