ArticleThe Biochemical journal2007
Hormonal regulation of the Menkes and Wilson copper-transporting ATPases in human placental Jeg-3 cells.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 66 citations in OpenAlex.
- Novel impact of metal ion-induced cell death on diabetic cardiomyopathy pathogenesis and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Salivary Zinc and Copper Levels Are Differentially Associated with ROS Levels in Breast Cancer Patients.International journal of molecular sciences · 2025Article
- Modeling human placental biology: a review of organoid technologies.Frontiers in cell and developmental biology · 2025Review
- Variations in Blood Copper and Possible Mechanisms During Pregnancy.Biological trace element research · 2024Review
- [Pregnancy management in patients with hepatolenticular degeneration].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Review
- Low Copper Diet-A Therapeutic Option for Wilson Disease?Children (Basel, Switzerland) · 2022Review
- Dynamic and cell-specific transport networks for intracellular copper ions.Journal of cell science · 2021Review
- The Role of Fe, Zn, and Cu in Pregnancy.Biomolecules · 2020Review
- Copper associates with differential methylation in placentae from two US birth cohorts.Epigenetics · 2020Article
- Copper transporters and copper chaperones: roles in cardiovascular physiology and disease.American journal of physiology. Cell physiology · 2018Review
- Akt2 (Protein Kinase B Beta) Stabilizes ATP7A, a Copper Transporter for Extracellular Superoxide Dismutase, in Vascular Smooth Muscle: Novel Mechanism to Limit Endothelial Dysfunction in Type 2 Diabetes Mellitus.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Effects of Octylphenol and Bisphenol A on the Metal Cation Transporter Channels of Mouse Placentas.International journal of environmental research and public health · 2016Article
- Copper trafficking to the secretory pathway.Metallomics : integrated biometal science · 2016Review
- Metal-Dependent Regulation of ATP7A and ATP7B in Fibroblast Cultures.Frontiers in molecular neuroscience · 2016Article
- Estrogen intake and copper depositions: implications for Alzheimer's disease?Case reports in neurology · 2014Article
- Article
- Advances in the understanding of mammalian copper transporters.Advances in nutrition (Bethesda, Md.) · 2011Review
- Mitochondrial iron trafficking and the integration of iron metabolism between the mitochondrion and cytosol.Proceedings of the National Academy of Sciences of the United States of America · 2010Review
- Cardiac copper deficiency activates a systemic signaling mechanism that communicates with the copper acquisition and storage organs.Cell metabolism · 2010Article
- Human copper homeostasis: a network of interconnected pathways.Current opinion in chemical biology · 2010Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Copper deficiency during pregnancy results in early embryonic death and foetal structural abnormalities including skeletal, pulmonary and cardiovascular defects. During pregnancy, copper is transported from the maternal circulation to the foetus by mechanisms which have not been clearly elucidated. Two copper-transporting ATPases, Menkes (ATP7A; MNK) and Wilson (ATP7B; WND), are expressed in the placenta and both are involved in placental copper transport, as copper accumulates in the placenta in both Menkes and Wilson disease. The regulatory mechanisms of MNK and WND and their exact role in the placenta are unknown. Using a differentiated polarized Jeg-3 cell culture model of placental trophoblasts, MNK and WND were shown to be expressed within these cells. Distinct roles for MNK and WND are suggested on the basis of their opposing responses to insulin. Insulin and oestrogen increased both MNK mRNA and protein levels, altered the localization of MNK towards the basolateral membrane in a copper-independent manner, and increased the transport of copper across this membrane. In contrast, levels of WND were decreased in response to insulin, and the protein was located in a tight perinuclear region, with a corresponding decrease in copper efflux across the apical membrane. These results are consistent with a model of copper transport in the placenta in which MNK delivers copper to the foetus and WND returns excess copper to the maternal circulation. Insulin and oestrogen stimulate copper transport to the foetus by increasing the expression of MNK and reducing the expression of WND. These data show for the first time that MNK and WND are differentially regulated by the hormones insulin and oestrogen in human placental cells.
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