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Hormonal regulation of the Menkes and Wilson copper-transporting ATPases in human placental Jeg-3 cells

Hardman, Belinda, Michalczyk, Agnes, Greenough, Mark, Camakaris, James, Mercer, Julian and Ackland, Leigh 2007, Hormonal regulation of the Menkes and Wilson copper-transporting ATPases in human placental Jeg-3 cells, Biochemical journal, vol. 402, no. 2, pp. 241-250, doi: 10.1042/BJ20061099.

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Title Hormonal regulation of the Menkes and Wilson copper-transporting ATPases in human placental Jeg-3 cells
Author(s) Hardman, Belinda
Michalczyk, AgnesORCID iD for Michalczyk, Agnes orcid.org/0000-0001-5716-0783
Greenough, Mark
Camakaris, James
Mercer, Julian
Ackland, LeighORCID iD for Ackland, Leigh orcid.org/0000-0002-7474-6556
Journal name Biochemical journal
Volume number 402
Issue number 2
Start page 241
End page 250
Publisher The Biochemical Society
Place of publication London, England
Publication date 2007
ISSN 0264-6021
1470-8728
Keyword(s) copper
insulin
Menkes disease
oestrogen
pregnancy
Wilson disease
Summary 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 coppertransporting 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 MNKand WNDand 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 forMNKandWND 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.
Language eng
DOI 10.1042/BJ20061099
Field of Research 060111 Signal Transduction
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2007, Biochemical Society
Persistent URL http://hdl.handle.net/10536/DRO/DU:30007159

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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