CCS and SOD1 mRNA are reduced after copper supplementation in peripheral mononuclear cells of individuals with high serum ceruloplasmin concentration.
The limits of copper homeostatic regulation in humans are not known, making it difficult to define the milder effects of early copper excess. Furthermore, a robust assay to facilitate the detection of early stages of copper excess is needed. To address these issues, we assessed changes in relative mRNA abundance of methallothionein 2A (MT2A), prion (PrP), amyloid precursor-like protein 2 (APLP2), Cu/Zn superoxide dismutase (SOD1) and its copper chaperone (CCS) in peripheral mononuclear cells (PMNCs) from healthy adults representing the 5% highest and lowest extremes in the distribution curve of serum ceruloplasmin (Cp) concentrations of 800 individuals. The intracellular Cu content was also determined. PMNCs were isolated from individuals before and after exposure to a single daily dose of 10 mg Cu (as CuSO(4)) for 2 months. Results showed that although there were fluctuations in serum Cp values of the samples assessed before copper exposure, no significant differences were observed in cell copper content or in the relative abundance of MT2A, PrP and APLP2 transcripts in PMNCs. Also, these values were not modified after copper supplementation. However, CCS and SOD1 mRNA levels were reduced in PMNCs after copper supplementation in the individuals with the high Cp values, suggesting that they should be further explored as biomarkers of moderate copper overload in humans.
Laboratory of Micronutrients, University of Chile (INTA), Santiago, Chile.
Miriam
M
Suazo
Felipe
F
Olivares
Marco A
MA
Mendez
Rodrigo
R
Pulgar
Joseph R
JR
Prohaska
Miguel
M
Arredondo
Fernando
F
Pizarro
Manuel
M
Olivares
Magdalena
M
Araya
Mauricio
M
González
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D002570:Ceruloplasmin / Q000032:analysis*; D003300:Copper / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
C084104:APLP2 protein, human; D016564:Amyloid beta-Protein Precursor; C114678:CCS protein, human; C491053:MT2A protein, human; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D011328:Prions; D012333:RNA, Messenger; C000606290:SOD1 protein, human; D003300:Copper; D008668:Metallothionein; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D002570:Ceruloplasmin