The role of subcutaneous adipose tissue in supporting the copper balance in rats with a chronic deficiency in holo-ceruloplasmin

• Published in: PloS one Vol. 12; no. 4; p. e0175214
• Main Authors: Ilyechova, Ekaterina Y, Tsymbalenko, Nadezhda V, Puchkova, Ludmila V
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05-04-2017; Public Library of Science (PLoS)
• Subjects: Absorption spectroscopy; Adipose tissue; Amino acids; Animals; Atomic absorption analysis; Atomic absorption spectroscopy; Bioaccumulation; Biology and Life Sciences; Body fat; Body mass; Centrifugation; Ceruloplasmin; Ceruloplasmin - deficiency; Ceruloplasmin - metabolism; Circulation; Copper; Copper (Nutrient); Copper - metabolism; Disease; Education; Female; Fodder; Forage; Gastrointestinal surgery; Gene expression; Genes; Glycosylphosphatidylinositol; Golgi apparatus; Hematology; Homeostasis; Immunoblotting; Immunoelectrophoresis; Immunoprecipitation; In vitro methods and tests; Iron; Isoforms; Male; Mammals; Medical research; Medicine and Health Sciences; Metabolism; Muscle, Skeletal - metabolism; Muscles; o-Dianisidine; Oxidase; Physical Sciences; Physiological aspects; Physiology; Polymerase chain reaction; Polypeptides; Rats; Rats, Wistar; Rodents; Silver; Silver - metabolism; Skeletal muscle; Spectral analysis; Spectrometry; Subcutaneous Fat - metabolism; Synthesis; Tissues; United Kingdom; Russia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0175214

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.