ArticleArchives of toxicology2020
In vitro function and in situ localization of Multidrug Resistance-associated Protein (MRP)1 (ABCC1) suggest a protective role against methyl mercury-induced oxidative stress in the human placenta.
Article in Archives of toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Mercury-induced excitotoxicity in autism spectrum disorder: disruption of glutamatergic homeostasis and the therapeutic role of the selenium-glutathione axis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Adenosine triphosphate-binding cassette transporters: key players in maintaining fetal health during pregnancy.Frontiers in endocrinology · 2026Review
- ABCC1 promotes GSH-dependent iron transport and resistance to Fe(II) and Cu(II) chelators.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Article
- Membrane transporters modulating the toxicity of arsenic, cadmium, and mercury in human cells.Life science alliance · 2025Article
- ABCC1 deficiency potentiated noise-induced hearing loss in mice by impairing cochlear antioxidant capacity.Redox biology · 2024Article
- Genetic factors in methylmercury-induced neurotoxicity: What have we learned fromAdvances in neurotoxicology · 2023Article
- Detection of Relevant Heavy Metal Concentrations in Human Placental Tissue: Relationship between the Concentrations of Hg, As, Pb and Cd and the Diet of the Pregnant Woman.International journal of environmental research and public health · 2022Article
- Regulation of Placental Efflux Transporters during Pregnancy Complications.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function.Biomolecules · 2022Article
- Transporter Regulation in Critical Protective Barriers: Focus on Brain and Placenta.Pharmaceutics · 2022Review
- Methylmercury exposure during prenatal and postnatal neurodevelopment promotes oxidative stress associated with motor and cognitive damages in rats: an environmental-experimental toxicology study.Toxicology reports · 2022Article
- Overview of Drug Transporters in Human Placenta.International journal of molecular sciences · 2021Review
- Amino Acid Transporter LAT1 (SLC7A5) Mediates MeHg-Induced Oxidative Stress Defense in the Human Placental Cell Line HTR-8/SVneo.International journal of molecular sciences · 2021Article
- Gene Variants Determine Placental Transfer of Perfluoroalkyl Substances (PFAS), Mercury (Hg) and Lead (Pb), and Birth Outcome: Findings From the UmMuKi Bratislava-Vienna Study.Frontiers in genetics · 2021Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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