BACKGROUND/AIMS: The copper transporting ATPases, Menkes (ATP7A; MNK) and Wilson (ATP7B; WND) are essential for normal copper transport in the human body. The placenta is the key organ in copper supply to the fetus during pregnancy and it is one of the few organs in the body to express both of the ATPases. The placenta therefore provides a unique opportunity to elucidate the specific roles of these transporters within the one cell type. METHODS/ RESULTS: Using polarized placental Jeg-3 cells, siRNA technology and radio-labelled 64Cu transport assays, MNK and WND were shown to have distinct roles in the vectorial transport of copper. MNK transported copper from the cell via the basolateral membrane and in contrast, WND transported copper from the apical membrane. Inactivation of MNK resulted in decreased activity of two important cuproenzymes, lysyl oxidase and Cu/Zn-superoxide dismutase. CONCLUSIONS: Overall, these results provide definitive evidence for distinct roles of MNK and WND in the human placenta, and are consistent with a role for MNK in the transport of copper into the fetal circulation, and through delivery of copper to placental cuproenzymes, whilst WND contributes to the maintenance of placental copper homeostasis by transporting copper to the maternal circulation.
BACKGROUND/AIMS: The copper transporting ATPases, Menkes (ATP7A; MNK) and Wilson (ATP7B; WND) are essential for normal copper transport in the human body. The placenta is the key organ in copper supply to the fetus during pregnancy and it is one of the few organs in the body to express both of the ATPases. The placenta therefore provides a unique opportunity to elucidate the specific roles of these transporters within the one cell type. METHODS/ RESULTS: Using polarized placental Jeg-3 cells, siRNA technology and radio-labelled 64Cu transport assays, MNK and WND were shown to have distinct roles in the vectorial transport of copper. MNK transported copper from the cell via the basolateral membrane and in contrast, WND transported copper from the apical membrane. Inactivation of MNK resulted in decreased activity of two important cuproenzymes, lysyl oxidase and Cu/Zn-superoxide dismutase. CONCLUSIONS: Overall, these results provide definitive evidence for distinct roles of MNK and WND in the human placenta, and are consistent with a role for MNK in the transport of copper into the fetal circulation, and through delivery of copper to placental cuproenzymes, whilst WND contributes to the maintenance of placental copper homeostasis by transporting copper to the maternal circulation.
Authors: Elizabeth Kennedy; Todd M Everson; Tracy Punshon; Brian P Jackson; Ke Hao; Luca Lambertini; Jia Chen; Margaret R Karagas; Carmen J Marsit Journal: Epigenetics Date: 2019-09-04 Impact factor: 4.528
Authors: Valentina Medici; Dorothy A Kieffer; Noreene M Shibata; Harpreet Chima; Kyoungmi Kim; Angela Canovas; Juan F Medrano; Alma D Islas-Trejo; Kusum K Kharbanda; Kristin Olson; Ruijun J Su; Mohammad S Islam; Raisa Syed; Carl L Keen; Amy Y Miller; John C Rutledge; Charles H Halsted; Janine M LaSalle Journal: Epigenetics Date: 2016-09-09 Impact factor: 4.528
Authors: Roxana M Llanos; Agnes A Michalczyk; David J Freestone; Scott Currie; Maria C Linder; M Leigh Ackland; Julian F B Mercer Journal: Biochem Biophys Res Commun Date: 2008-06-02 Impact factor: 3.575
Authors: Agnes Michalczyk; Edward Bastow; Mark Greenough; James Camakaris; David Freestone; Philip Taylor; Maria Linder; Julian Mercer; Margaret L Ackland Journal: J Histochem Cytochem Date: 2008-01-07 Impact factor: 2.479