title: Transcuprein is a macroglobulin regulated by copper and iron availability.
abstract: Transcuprein is a high-affinity copper carrier in the plasma that is involved in the initial distribution of copper entering the blood from the digestive tract. To identify and obtain cDNA for this protein, it was purified from rat plasma by size exclusion and copper-chelate affinity chromatography, and amino acid sequences were obtained. These revealed a 190-kDa glycosylated protein identified as the macroglobulin alpha(1)-inhibitor III, the main macroglobulin of rodent blood plasma. Albumin (65 kDa) copurified in variable amounts and was concluded to be a contaminant (although it can transiently bind the macroglobulin). The main macroglobulin in human blood plasma (alpha(2)-macroglobulin), which is homologous to alpha(1)-inhibitor III, also bound copper tightly. Expression of alpha(1)I3 (transcuprein) mRNA by the liver was examined in rats with and without copper deficiency, using quantitative polymerase chain reaction methodology and Northern blot analysis. Protein expression was examined by Western blotting. Deficient rats with 40% less ceruloplasmin oxidase activity and liver copper concentrations expressed about twice as much alpha(1)I3 mRNA, but circulating levels of transcuprein did not differ. Iron deficiency, which increased liver copper concentrations by threefold, reduced transcuprein mRNA expression and circulating levels of transcuprein relative to what occurred in rats with normal or excess iron. We conclude that transcupreins are specific macroglobulins that not only carry zinc but also carry transport copper in the blood, and that their expression can be modulated by copper and iron availability.
authors.affiliation: Department of Chemistry and Biochemistry, California State University, Fullerton, CA 92834-6866, USA.
authors.forename: Nanmei
authors.initials: N
authors.lastname: Liu
authors.forename: Louis Shi-li
authors.initials: LS
authors.lastname: Lo
authors.forename: S Hassan
authors.initials: SH
authors.lastname: Askary
authors.forename: LaTrice
authors.initials: L
authors.lastname: Jones
authors.forename: Theodros Z
authors.initials: TZ
authors.lastname: Kidane
authors.forename: Trisha
authors.initials: T
authors.lastname: Trang
authors.forename: Minh
authors.initials: M
authors.lastname: Nguyen
authors.forename: Jeremy
authors.initials: J
authors.lastname: Goforth
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Chu
authors.forename: Esther
authors.initials: E
authors.lastname: Vivas
authors.forename: Monta
authors.initials: M
authors.lastname: Tsai
authors.forename: Terence
authors.initials: T
authors.lastname: Westbrook
authors.forename: Maria C
authors.initials: MC
authors.lastname: Linder
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D003300:Copper / Q000097:blood / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism*; D019266:Iron, Dietary / Q000008:administration & dosage; D008259:Macroglobulins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009752:Nutritional Status; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020539:Sequence Analysis, Protein; D000511:alpha-Macroglobulins / Q000235:genetics / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary; D019266:Iron, Dietary; D008259:Macroglobulins; D021122:Protein Subunits; D012333:RNA, Messenger; C017894:alpha 1-inhibitor 3; D000511:alpha-Macroglobulins; C023548:copper-binding protein; D003300:Copper; D007501:Iron