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Transcupreins are serum copper‐transporters of the macroglobulin family, and may be regulated by iron and copper
Author(s) -
Liu Nanmei,
Nguyen Trang,
Kidane Theodros,
Moriya Mizue,
Goforth Jeremy,
Chu Andy,
Linder Maria
Publication year - 2006
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.20.4.a553-d
Subject(s) - ceruloplasmin , albumin , macroglobulin , chemistry , oxidase test , messenger rna , copper , protein subunit , affinity chromatography , microbiology and biotechnology , transporter , biochemistry , medicine , biology , enzyme , gene , organic chemistry
As first demonstrated in rats, transcuprein is a high affinity serum Cu carrier involved in the initial distribution of Cu entering the blood from the digestive tract. To obtain cDNA for this protein, it was purified from rat plasma by size exclusion and Cu chelate affinity chromatography. Amino acid sequencing revealed that it was the rodent macroglobulin, a 1 inhibitorIII (a 1 I3). A second potential albumin‐like subunit (65 kDa) was shown to be a contaminant. The homologous protein in human serum, alpha‐ 2 ‐macroglobulin (a2M), also bound Cu and (like a 1 I3) did so more tightly than albumin, which has a high affinity N‐terminal binding site. Based on size exclusion chromatography, the proportion of total serum Cu associated with transcuprein in rats and humans was 10–15%. Delivery of Cu to human hepatic (Hep G2) cells by transcuprein (Cu bound to a2M) resulted in efficient uptake. Expression of a 1 I3 mRNA by the liver was examined in rats with and without Cu deficiency, using quantitative PCR and Northern analysis. Deficient rats with 40% less ceruloplasmin oxidase activity and liver Cu expressed about twice as much transcuprein mRNA. Iron deficiency, which increased liver Cu concentrations, reduced transcuprein mRNA expression and circulating levels of transcuprein relative to what occurred in rats with normal or excess Fe. We conclude that transcupreins are specific macroglobulin involved in the blood transport of Cu, and that their expression is related to copper and iron availability. Supported in part by PHS Grants No. HD46949 and IR24 CA86307.