Modulation of synthesis of specific proteins in endothelial cells by copper, cadmium, and disulfiram: an early response to an angiogenic inducer of cell migration.
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.
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
D005353:Fibronectins; D002104:Cadmium; D003300:Copper; D004221:Disulfiram