Ceruloplasmin is regulated by copper and lactational hormones in PMC42-LA mammary epithelial cell culture models

Freestone, David, Denoyer, Delphine, Jakab, Matthew, Ackland, M. Leigh, Cater, Michael and Michalczyk, Agnes 2016, Ceruloplasmin is regulated by copper and lactational hormones in PMC42-LA mammary epithelial cell culture models, Metallomics, vol. 8, no. 9, pp. 941-950, doi: 10.1039/c6mt00086j.

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Title Ceruloplasmin is regulated by copper and lactational hormones in PMC42-LA mammary epithelial cell culture models
Author(s) Freestone, David
Denoyer, DelphineORCID iD for Denoyer, Delphine orcid.org/0000-0001-8932-5116
Jakab, Matthew
Ackland, M. LeighORCID iD for Ackland, M. Leigh orcid.org/0000-0002-7474-6556
Cater, Michael
Michalczyk, AgnesORCID iD for Michalczyk, Agnes orcid.org/0000-0001-5716-0783
Journal name Metallomics
Volume number 8
Issue number 9
Start page 941
End page 950
Total pages 10
Publisher Royal Society of Chemistry
Place of publication Cambridge, Eng.
Publication date 2016-09-01
ISSN 1756-591X
Summary Ceruloplasmin (Cp) is a multicopper ferroxidase that is considered to be an important source of copper in milk for normal neonatal development. We investigated the expression, subcellular localization and secretion of Cp in PMC42-LA cell culture models representative of resting, lactating and suckled human mammary epithelia. Both secreted Cp (sCp) and plasma membrane associated glycosylphosphatidylinositol-linked Cp (GPI-Cp) were expressed in PMC42-LA cells. In all three epithelial models (resting, lactating and suckled), the expression and secretion of copper-bound, ferroxidase active, Cp (holo-Cp) was dependent on media copper concentration. In low copper (bathocuproinedisulphonic acid/d-penicillamine treated models) there was greater than a 2-fold decrease in holo-Cp expression and secretion, which was mirrored by a 2-fold increase in the expression and secretion of copper-free Cp protein (apo-Cp). Cell surface biotinylation studies revealed that the state of PMC42-LA cell differentiation (functionality), and the level of extracellular copper, had no significant effect on the level of plasma membrane bound GPI-Cp. Quantitative real time PCR analyses determined that there was no significant (P > 0.05) difference in Cp mRNA levels across all copper conditions investigated (0, 5, 50 μM). However, there was a significant (P < 0.05) increase (∼2-fold) in Cp mRNA in both the lactating and suckled models in comparison to the resting model. Furthermore, the Cp mRNA increase in response to PMC42-LA differentiation corresponded with more secreted Cp protein, both apo and holo forms, indicating a link between function and Cp requirement. Our results provide significant insight on the regulation of Cp expression and secretion in lactation and copper incorporation into milk.
Language eng
DOI 10.1039/c6mt00086j
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, The Royal Society of Chemistry
Persistent URL http://hdl.handle.net/10536/DRO/DU:30085296

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