Ceruloplasmin gene expression profile changes in the rat mammary gland during pregnancy, lactation and involution

• Published in: Journal of trace elements in medicine and biology 2017-09, Vol.43, p.126-134
• Main Authors: Platonova, Natalia A., Orlov, Iurii A., Klotchenko, Sergey A., Babich, Victor S., Ilyechova, Ekaterina Y., Babich, Polina S., Garmai, Yuri P., Vasin, Andrey V., Tsymbalenko, Nadezhda V., Puchkova, Liudmila V.
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Western; Cell Membrane - metabolism; Ceruloplasmin - genetics; Ceruloplasmin - metabolism; Ceruloplasmin gene splice forms; Copper metabolism; Copper transporting ATPases; Copper-transporting ATPases - genetics; Copper-transporting ATPases - metabolism; Female; Growth-regression cycle of mammary gland; High affinity copper importer 1; Humans; Lactation - genetics; Lactation - metabolism; Mammary Glands, Human - metabolism; Pregnancy; Rats
• ISSN: 0946-672X; 1878-3252
• DOI: 10.1016/j.jtemb.2016.12.013

[Display omitted] •Ratios between the Cp-mRNA splice forms are regulated during mammary glands cycle.•Expression of ATP7A and ATP7B is correlated with GPI- and sCp levels, respectively.•ATP7A protein localizes in plasma membrane of mammary gland cells during pregnancy.•ATP7B localizes in plasma membrane of lactating mammary gland cells.•PreCp-mRNA maturation is violated due to splicing disturbances during involution. Copper metabolism disturbances in mammary gland (MG) cells have severe consequences in newborns. The mechanism that controls the balance of copper in the MG has not been thoroughly characterized. Four primary copper homeostasis genes in mammals: (1) ceruloplasmin (Cp) encoding multifunction multicopper blue (ferr)oxidase; (2) CTR1 encoding high affinity copper importer 1; and (3 and 4) two similar genes encoding Cu(I)/Cu(II)-ATPases P1 type (ATP7A and ATP7B) responsible for copper efflux from the cells and metallation of cuproenzymes formed in the Golgi complex are expressed in MG. This study aimed to characterize expression of these genes during pregnancy, lactation and forced involution in the rat MG. We found that Cp anchored to the plasma membrane and ATP7A were expressed during pregnancy and lactation. Soluble Cp and ATP7B were highly expressed in lactating MG decreasing to its ending. CTR1 activity increased during MG growth and reached its maximum at postpartum and then it decreased until the end of lactation. During early forced MG involution, Cp gene expression persisted; while a form of Cp that lacked exon 18 appeared. We suggest that Cp gene expressional changes at the transcriptional and posttranscriptional level reflect various physiological functions of Cp proteins during MG remodeling.