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

International Journal of Molecular Sciences

Herbert Stangl¹  Raimund Widhalm²  Christina Balthasar²  Claudia Gundacker²  Markus Hengstschläger²  Sebastian Granitzer² 

[1] Center for Pathobiochemistry and Genetics, Institute of Medical Chemistry, Währinger Strasse 10, Medical University of Vienna, 1090 Wien, Vienna, Austria;Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Währinger Strasse 10, Medical University of Vienna, 1090 Wien, Vienna, Austria;

关键词: methylmercury;    leucine;    methionine;    human placenta;    SLC7A5;    SLC7A8;    SLC3A2;    Forskolin;   

DOI  :  10.3390/ijms18081730

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown