Reconstitution of the intercellular transfer pathway of the peptide moiety of ceruloplasmin in mammals.
According to rocket immunoelectrophoresis, the antigenic properties of the ceruloplasmin (Cp) receptor present on the surface of human fibroblasts are similar to those of the Cp receptor of the erythrocyte plasma membrane. Using antibodies to Cp receptor, it was demonstrated that Cp binds to the surface of fibroblasts only via the Cp receptor. Ceruloplasmin was labelled with radioactive iodine and its binding to cultured human HT-1080 fibroblasts was studied; at saturating concentrations [125I]Cp interacts with cell surface of fibroblasts (but not hepatocytes) with high affinity (Kd = 80 nM). Subsequent to specific binding fibroblasts absorb [125I]Cp and in about 120-150 min start to release it into the incubation medium. Two fractions of released Cp are clearly detected by non-denaturing polyacrylamide gel electrophoresis. The relative mobility of one of these fractions corresponds to apo-Cp and the other has lower mobility than native Cp. The molecular weight of released [125I]Cp is changed insignificantly. Released Cp does not bind again to the fibroblast surface but is bound, absorbed, degraded, and secreted by hepatocytes. The molecular mechanism of cell-specific transfer of Cp in the human body is discussed and possible functions of this mechanism in copper absorption, metabolism, and excretion in mammals are considered.
Puchkova
L V
LV
Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia. ludmila@usr8.iem.ras.spb.ru
Sasina
L K
LK
Aleinikova
T D
TD
Zakharova
E T
ET
Gaitskhoki
V S
VS
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001693:Biological Transport, Active; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002570:Ceruloplasmin / Q000737:chemistry* / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D004705:Endocytosis; D004912:Erythrocytes / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism
D037263:Asialoglycoprotein Receptor; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; C040519:ceruloplasmin receptor; D003300:Copper; D002570:Ceruloplasmin