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Relation of Copper Toxicosis in Dogs and Wilson Disease to the Appearance of a Small Copper Carrier (SCC) in Blood Plasma and Urine
Author(s) -
Flynn Stephen,
Dalphin Matthew,
Tellez Miguel,
Fieten Hille,
Weldy Scott,
Muchenditsi Abigael,
Lutsenko Svetlana,
Linder Maria
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.921.2
Subject(s) - ceruloplasmin , copper , excretion , wilson's disease , urine , medicine , blood proteins , endocrinology , chemistry , metabolism , copper metabolism , biology , biochemistry , disease , organic chemistry
The main route for copper excretion in mammals is via the bile, little exiting through urine. In Wilson disease, biliary excretion is prevented by lack of an active form of ATP7B, which permits copper entry into bile. This leads to copper accumulation and severe liver toxicosis. Dogs tend to have the same problem, with much higher liver copper levels than other mammals. Many die of liver copper toxicosis. As in Wilson disease, Atp7b‐/‐ mice excrete high levels of copper in urine. Excretion is in the form of a 1.5 kDa SCC. We now have evidence that the same SCC exists in the blood plasma of humans, mice and dogs. Normally, it is bound to larger proteins, but large amounts of free SCC occur in the plasma of Atp7b‐/‐ mice, and in some dogs. SCC can be released from larger proteins by EDTA and accounts for ~10% of the total copper in human plasma. SCC is also released by EDTA in plasma from dogs and mice, including those with “free” SCC. FPLC‐SEC preliminary data suggest SCC is riding on proteins >200kDa. Dog ceruloplasmin is also unusual, eluting as a much larger protein, although of normal size in SDS‐PAGE. We conclude that SCC may offer an alternative route for copper excretion that can be mobilized in some mammals in response to liver copper accumulation, and that the study of dog plasma may reveal additional information about copper metabolism not detected as easily in other species.