title: Copper metabolism in hypercupremic human livers. Studies of its subcellular distribution, association with binding proteins and expression of mRNAs.
abstract: In the present study we have used differential centrifugation, size exclusion chromatography, Western and Northern blotting to investigate the subcellular distribution of hepatic copper, the association of the metal with hepatic copper binding proteins and the expression of specific mRNAs for copper binding proteins in liver tissue from two patients with Wilson's disease, two patients with chronic liver disease and two patients with normal hepatic copper levels. Unlike previous studies the present results fail to show any gross differences in subcellular distribution of copper between the livers, with most of the copper being found in the soluble supernatant where it is associated with metallothionein. Caeruloplasmin mRNA levels were reduced in the two patients with Wilson's disease and also in a patient with fulminant hepatic failure. It remains to be confirmed if the reduction of caeruloplasmin mRNA is specific for Wilson's disease. Levels of mRNAs for copper zinc superoxide dismutase and metallothionein were variable and not related to liver copper.
authors.affiliation: Department of Protein and Molecular Biology, Royal Free Hospital School of Medicine, London, United Kingdom.
authors.forename: C D
authors.initials: CD
authors.lastname: Bingle
authors.forename: S K
authors.initials: SK
authors.lastname: Srai
authors.forename: O
authors.initials: O
authors.lastname: Epstein
mesh_terms: D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002458:Cell Fractionation; D002498:Centrifugation; D002570:Ceruloplasmin / Q000235:genetics / Q000378:metabolism; D002850:Chromatography, Gel; D003300:Copper / Q000032:analysis / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D006527:Hepatolenticular Degeneration / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D012333:RNA, Messenger; D003300:Copper; D008668:Metallothionein; D013482:Superoxide Dismutase; D002570:Ceruloplasmin