INTERACTION OF HUMAN ANGIOGENIN WITH COPPER MODULATES ANGIOGENIN BINDING TO ENDOTHELIAL-CELLS

Angiogenin is a potent inducer of blood-vessel formation with ribonucl eolytic activity. Angiogenin binds to high affinity endothelial cell r eceptors and with lower affinity to extracellular matrix components. H ere we report the effect of copper and zinc on these interactions. The re was a 4.3-fold increase in angiogenin binding to calf pulmonary art ery endothelial cells in the presence of Cu2+ in vitro. A 3.8-fold inc rease was observed with Zu(2+), whereas Ni2+, Co2+, or Li+ had no effe ct. Specific angiogenin binding to the lower affinity matrix sites was increased by 2.7- and 1.9-fold in the presence of Cu2+ and Zn2+ respe ctively. Metal ion affinity chromatography and atomic absorption spect rometry were used to show the direct interaction of angiogenin with co pper and zinc ions. Angiogenin bound 2.4 mol of copper per mole of pro tein. We suggest that copper, a modulator of angiogenesis in vivo, may be involved in the regulation of the biological activity of angiogeni n. (C) 1997 Academic Press.