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Methylmercury Uptake into BeWo Cells Depends on LAT2-4F2hc, a System L Amino Acid Transporter.

التفاصيل البيبلوغرافية
العنوان: Methylmercury Uptake into BeWo Cells Depends on LAT2-4F2hc, a System L Amino Acid Transporter.
المؤلفون: Balthasar C; Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Währinger Strasse 10, Medical University of Vienna, 1090 Wien, Vienna, Austria. christina.balthasar@gmail.com., Stangl H; Center for Pathobiochemistry and Genetics, Institute of Medical Chemistry, Währinger Strasse 10, Medical University of Vienna, 1090 Wien, Vienna, Austria. herbert.stangl@meduniwien.ac.at., Widhalm R; Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Währinger Strasse 10, Medical University of Vienna, 1090 Wien, Vienna, Austria. raimund.widhalm@meduniwien.ac.at., Granitzer S; Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Währinger Strasse 10, Medical University of Vienna, 1090 Wien, Vienna, Austria. Sebastian.Granitzer@kl.ac.at.; Karl Landsteiner University of Health Sciences, Dr.-Karl-Dorrek-Straße 30, 3500 Krems an der Donau, Austria. Sebastian.Granitzer@kl.ac.at., Hengstschläger M; Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Währinger Strasse 10, Medical University of Vienna, 1090 Wien, Vienna, Austria. markus.hengstschlaeger@meduniwien.ac.at., Gundacker C; Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Währinger Strasse 10, Medical University of Vienna, 1090 Wien, Vienna, Austria. claudia.gundacker@meduniwien.ac.at.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2017 Aug 08; Vol. 18 (8). Date of Electronic Publication: 2017 Aug 08.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Amino Acid Transport System L/*metabolism , Methylmercury Compounds/*metabolism, Amino Acid Transport System L/genetics ; Cell Line, Tumor ; Colforsin/pharmacology ; Gene Expression Regulation/drug effects ; Humans ; Large Neutral Amino Acid-Transporter 1/genetics ; Leucine/metabolism ; Methionine/metabolism
مستخلص: The organic mercury compound methylmercury (MeHg) is able to target the fetal brain. However, the uptake of the toxicant into placental cells is incompletely understood. MeHg strongly binds to thiol-S containing molecules such as cysteine. This MeHg-l-cysteine exhibits some structural similarity to methionine. System L plays a crucial role in placental transport of essential amino acids such as leucine and methionine and thus has been assumed to also transport MeHg-l-cysteine across the placenta. The uptake of methylmercury and tritiated leucine and methionine into the choriocarcinoma cell line BeWo was examined using transwell assay and small interfering (si)RNA mediated gene knockdown. Upon the downregulation of large neutral amino acids transporter (LAT)2 and 4F2 cell-surface antigen heavy chain (4F2hc), respectively, the levels of [³H]leucine in BeWo cells are significantly reduced compared to controls treated with non-targeting siRNA ( p < 0.05). The uptake of [³H]methionine was reduced upon LAT2 down-regulation as well as methylmercury uptake after 4F2hc silencing ( p < 0.05, respectively). These findings suggest an important role of system L in the placental uptake of the metal. Comparing the cellular accumulation of mercury, leucine, and methionine, it can be assumed that (1) MeHg is transported through system L amino acid transporters and (2) system L is responsible for the uptake of amino acids and MeHg primarily at the apical membrane of the trophoblast. The findings together can explain why mercury in contrast to other heavy metals such as lead or cadmium is efficiently transported to fetal blood.
Competing Interests: The authors declare no conflict of interest.
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فهرسة مساهمة: Keywords: Forskolin; SLC3A2; SLC7A5; SLC7A8; human placenta; leucine; methionine; methylmercury
المشرفين على المادة: 0 (Amino Acid Transport System L)
0 (Large Neutral Amino Acid-Transporter 1)
0 (Methylmercury Compounds)
1F7A44V6OU (Colforsin)
AE28F7PNPL (Methionine)
GMW67QNF9C (Leucine)
تواريخ الأحداث: Date Created: 20170809 Date Completed: 20180423 Latest Revision: 20181113
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC5578120
DOI: 10.3390/ijms18081730
PMID: 28786956
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms18081730