title: Modulation of synthesis of specific proteins in endothelial cells by copper, cadmium, and disulfiram: an early response to an angiogenic inducer of cell migration.
abstract: Copper, cadmium, and disulfiram (an ionophore for copper) modulate the synthesis of several polypeptides in two clonal lines of bovine aortal endothelial cells. After treatment of Type 1 endothelial cells with 10(-3) M CuSO4 or 10(-5) M CdCl2 four cell-associated polypeptides (Mr = 28,000, 32,000, 73,000, and 83,000 daltons) were induced. In contrast, in Type 2 endothelial cells, which have cultural characteristics distinct from Type 1, only one new cell-associated protein (Mr = 32,000 daltons) was induced by CuSO4 or CdCl2. The same four polypeptides, described above, were induced by disulfiram (10(-7) M) in Type 1 endothelial cells. In contrast when Type 2 endothelial cells were treated with disulfiram the synthesis of only two new cell-associated proteins (Mr = 32,000 and 40,000 daltons) was induced. Other differences are revealed by analyses of proteins secreted into the growth medium. In particular low levels of only CuSO4 (10(-6) M) enhanced the synthesis in Type 2 cells of a protein (Mr = 220,000 daltons) identified as fibronectin. Since only copper ions induced fibronectin, we propose that the mechanism of induction of fibronectin synthesis, in contrast to the induction of cell-associated polypeptides, does not involve a sulphydryl-containing receptor molecule. It is suggested that the specific enhancement of fibronectin synthesis by copper ions may be a controlling event in the stimulation by copper ions of endothelial cell migration and angiogenesis.
mesh_terms: D000818:Animals; D001011:Aorta; D002104:Cadmium / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D002465:Cell Movement; D002999:Clone Cells; D003300:Copper / Q000494:pharmacology*; D004221:Disulfiram / Q000494:pharmacology*; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000096:biosynthesis; D008970:Molecular Weight; D009389:Neovascularization, Pathologic; D014176:Protein Biosynthesis
chemical_list: D005353:Fibronectins; D002104:Cadmium; D003300:Copper; D004221:Disulfiram