Effect of albumin on net copper accumulation by fibroblasts and hepatocytes.
The liver accumulates copper rapidly and preferentially from plasma. The effects of albumin on net copper accumulation by fibroblasts and hepatocytes were compared to determine whether preferential uptake involves hepatocyte-specific sequestering of copper. Although albumin inhibits the initial rates (30 s) of copper transport by fibroblasts and hepatocytes similarly, the effects of albumin on net copper accumulation (4 h) by these cell types were strikingly different. Fibroblasts accumulate only approximately 15% as much copper when equimolar albumin is present as from albumin-free media; hepatocytes accumulate about the same amount of copper with or without extracellular albumin present. Copper efflux data show that the special capacity of hepatocytes to accumulate copper in the presence of extracellular albumin is due to greater copper retention by hepatocytes than fibroblasts. The ability of hepatocytes to accumulate copper does not seem to be due to albumin-receptor-mediated uptake, since albumin was not co-transported with copper. The data are consistent with an equilibrium model of copper accumulation in which intracellular and extracellular copper are in equilibrium with intracellular and extracellular ligands. A high-affinity, copper-binding fraction that was previously identified in cytosols from hepatocytes was low or absent in fibroblasts. This may contain a liver-specific protein(s) that helps hepatocytes sequester and retain copper from albumin or serum-containing media. Irrespective of the exact species involved, the data are consistent with rapid, preferential copper uptake by the liver being due in part to a liver-specific, intracellular copper-binding protein(s) with a high binding affinity for copper.
Waldrop
G L
GL
Department of Biochemistry, State University of New York, Buffalo 14214.
Palida
F A
FA
Hadi
M
M
Lonergan
P A
PA
Ettinger
M J
MJ
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000378:metabolism*; D003301:Copper Radioisotopes; D003600:Cytosol / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D003301:Copper Radioisotopes; D012709:Serum Albumin; D003300:Copper