title: The role of subcutaneous adipose tissue in supporting the copper balance in rats with a chronic deficiency in holo-ceruloplasmin.
abstract: We have previously shown that (1) an acute deficiency in blood serum holo-ceruloplasmin (Cp) developed in rats that were fed fodder containing silver ions (Ag-fodder) for one month and (2) the deficiency in holo-Cp was compensated by non-hepatic holo-Cp synthesis in rats that were chronically fed Ag-fodder for 6 months (Ag-rats). The purpose of the present study is to identify the organ(s) that compensate for the hepatic holo-Cp deficiency in the circulation. This study was performed on rats that were fed Ag-fodder (40 mg Ag·kg-1 body mass daily) for 6 months. The relative expression levels of the genes responsible for copper status were measured by RT-PCR. The in vitro synthesis and secretion of [14C]Cp were analyzed using a metabolic labeling approach. Oxidase activity was determined using a gel assay with o-dianisidine. Copper status and some hematological indexes were measured. Differential centrifugation, immunoblotting, immunoelectrophoresis, and atomic absorption spectrometry were included in the investigation. In the Ag-rats, silver accumulation was tissue-specific. Skeletal muscles and internal (IAT) and subcutaneous (SAT) adipose tissues did not accumulate silver significantly. In SAT, the mRNAs for the soluble and glycosylphosphatidylinositol-anchored ceruloplasmin isoforms were expressed, and their relative levels were increased two-fold in the Ag-rats. In parallel, the levels of the genes responsible for Cp metallation (Ctr1 and Atp7a/b) increased correspondingly. In the SAT of the Ag-rats, Cp oxidase activity was observed in the Golgi complex and plasma membrane. Moreover, full-length [14C]Cp polypeptides were released into the medium by slices of SAT. The possibilities that SAT is part of a system that controls the copper balance in mammals, and it plays a significant role in supporting copper homeostasis throughout the body are discussed.
authors.affiliation: Department of Molecular Genetics, Institute of Experimental Medicine, St. Petersburg, Russia.|International Research and Education Center "Functional materials and devices of optoelectronics and microelectronics", ITMO University, St. Petersburg, Russia.
authors.forename: Ekaterina Y
authors.identifier: http://orcid.org/0000-0002-5623-2156
authors.initials: EY
authors.lastname: Ilyechova
authors.affiliation: Department of Molecular Genetics, Institute of Experimental Medicine, St. Petersburg, Russia.|International Research and Education Center "Functional materials and devices of optoelectronics and microelectronics", ITMO University, St. Petersburg, Russia.
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Tsymbalenko
authors.affiliation: Department of Molecular Genetics, Institute of Experimental Medicine, St. Petersburg, Russia.|International Research and Education Center "Functional materials and devices of optoelectronics and microelectronics", ITMO University, St. Petersburg, Russia.|Department of Biophysics, Institute of Physics, Nanotechnology, and Telecommunications, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia.
authors.forename: Ludmila V
authors.initials: LV
authors.lastname: Puchkova
mesh_terms: D000818:Animals; D002570:Ceruloplasmin / Q000172:deficiency* / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D005260:Female; D015151:Immunoblotting; D047468:Immunoprecipitation; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012834:Silver / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism*
chemical_list: D012834:Silver; D003300:Copper; D002570:Ceruloplasmin