Copper (II) ions modulate Angiogenin activity in human endothelial cells

Angiogenin (ANG), a member of the secreted ribonuclease family, is a potent angiogenesis stimulator that interacts with endothelial cells inducing a wide range of responses. Metal ions dyshomeostasis play a fundamental role in the onset of neurodegenerative diseases, in particular copper that is also involved in angiogenesis processes. It is known that vascular pathologies are present in neurodegenerative diseases and Angiogenin is down-regulated in Alzheimer and Parkinson diseases, as well as it has been found as one of the mutated genes in amyotrophic lateral sclerosis (ALS). Copper (II) induces an increase of Angiogenin binding to endothelial cells but, so far, the relationship between copper-ANG and angiogenesis induction remain unclear. Herein, the effects of copper (II) ions on Angiogenin activity and expression were evaluated. The binding of copper was demonstrated to affect the intracellular localization of the protein decreasing its nuclear translocation. Moreover, the ANG-copper (II) system negatively affects the protein-induced angiogenesis, as well as endothelial cells migration. Surprisingly, copper also reveals the ability to modulate the Angiogenin transcription. These results highlight the tight relationship between copper and Angiogenin, pointing out the biological relevance of ANG-copper system in the regulation of endothelial cell function, and revealing a possible new mechanism at the basis of vascular pathologies. (C) 2015 Elsevier Ltd. All rights reserved.