Methyl mercury (MeHg) is an organic highly toxic compound that is transported efficiently via the human placenta. Our previous data suggest that MeHg is taken up into placental cells by amino acid transporters while mercury export from placental cells mainly involves ATP binding cassette (ABC) transporters. We hypothesized that the ABC transporter multidrug resistance-associated protein (MRP)1 (ABCC1) plays an essential role in mercury export from the human placenta. Transwell transport studies with MRP1-overexpressing Madin-Darby Canine Kidney (MDCK)II cells confirmed the function of MRP1 in polarized mercury efflux. Consistent with this, siRNA-mediated MRP1 gene knockdown in the human placental cell line HTR-8/SVneo resulted in intracellular mercury accumulation, which was associated with reduced cell viability, accompanied by increased cytotoxicity, apoptosis, and oxidative stress as determined via the glutathione (GSH) status. In addition, the many sources claiming different localization of MRP1 in the placenta required a re-evaluation of its localization in placental tissue sections by immunofluorescence microscopy using an MRP1-specific antibody that was validated in-house. Taken together, our results show that (1) MRP1 preferentially mediates apical-to-basolateral mercury transport in epithelial cells, (2) MRP1 regulates the GSH status of placental cells, (3) MRP1 function has a decisive influence on the viability of placental cells exposed to low MeHg concentrations, and (4) the in situ localization of MRP1 corresponds to mercury transport from maternal circulation to the placenta and fetus. We conclude that MRP1 protects placental cells from MeHg-induced oxidative stress by exporting the toxic metal and by maintaining the placental cells' GSH status in equilibrium.

• MeSH
• ABC transportéry metabolismus   MeSH
• apoptóza účinky léků   MeSH
• buněčné linie MeSH
• buňky MDCK MeSH
• endoteliální buňky MeSH
• genový knockdown MeSH
• glutathion metabolismus   MeSH
• imunohistochemie MeSH
• kultivované buňky MeSH
• lidé MeSH
• methylortuťné sloučeniny škodlivé účinky   metabolismus   MeSH
• oxidační stres * MeSH
• placenta metabolismus   MeSH
• proteiny spojené s mnohočetnou rezistencí k lékům fyziologie   MeSH
• psi MeSH
• těhotenství MeSH
• transportní systémy aminokyselin metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• psi MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Total mercury (Hg) concentrations in hair and urine are often used as biomarkers of exposure to fish-derived methylmercury (MeHg) and gaseous elemental Hg, respectively. We used Hg stable isotopes to assess the validity of these biomarkers among small-scale gold mining populations in Ghana and Indonesia. Urine from Ghanaian miners displayed similar Δ(199)Hg values to Hg derived from ore deposits (mean urine Δ(199)Hg=0.01‰, n=6). This suggests that urine total Hg concentrations accurately reflect exposure to inorganic Hg among this population. Hair samples from Ghanaian miners displayed low positive Δ(199)Hg values (0.23-0.55‰, n=6) and low percentages of total Hg as MeHg (7.6-29%, n=7). These data suggest that the majority of the Hg in these miners' hair samples is exogenously adsorbed inorganic Hg and not fish-derived MeHg. Hair samples from Indonesian gold miners who eat fish daily displayed a wider range of positive Δ(199)Hg values (0.21-1.32‰, n=5) and percentages of total Hg as MeHg (32-72%, n=4). This suggests that total Hg in the hair samples from Indonesian gold miners is likely a mixture of ingested fish MeHg and exogenously adsorbed inorganic Hg. Based on data from both populations, we suggest that total Hg concentrations in hair samples from small-scale gold miners likely overestimate exposure to MeHg from fish consumption.

• MeSH
• biologické markery analýza   metabolismus   moč   MeSH
• dospělí MeSH
• hmotnostní spektrometrie MeSH
• hornictví * MeSH
• izotopy rtuti analýza   metabolismus   moč   MeSH
• látky znečišťující půdu analýza   metabolismus   moč   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methylortuťné sloučeniny analýza   metabolismus   moč   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• monitorování životního prostředí MeSH
• pracovní expozice * MeSH
• rtuť analýza   metabolismus   moč   MeSH
• ryby metabolismus   MeSH
• vlasy, chlupy chemie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Ghana MeSH
• Indonésie MeSH

• Klíčová slova
• vylučování rtuti žlučí,
• MeSH
• akademie a ústavy organizace a řízení   trendy   využití   MeSH
• epidemiologie organizace a řízení   trendy   MeSH
• experimenty na zvířatech * MeSH
• hygiena MeSH
• krysa rodu rattus MeSH
• methylortuťné sloučeniny metabolismus   škodlivé účinky   MeSH
• otrava rtutí * MeSH
• sloučeniny rtuti metabolismus   škodlivé účinky   MeSH
• statistika jako téma MeSH
• toxikologie metody   MeSH
• žluč * metabolismus   účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH