title: ♦Copper (II) ions modulate Angiogenin activity in human endothelial cells.
abstract: 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.
authors.affiliation: Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Giacomelli
authors.affiliation: Department of Pharmacy, University of Pisa, 56126 Pisa, Italy. Electronic address: maria.trincavelli@for.unipi.it.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Trincavelli
authors.affiliation: Department of Chemical Sciences, University of Catania, Viale Andrea Doria, 6, I-95125 Catania, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Satriano
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, PO Box 462, SE-40530 Gothenburg, Sweden.
authors.forename: Örjan
authors.initials: Ö
authors.lastname: Hansson
authors.affiliation: Department of Pharmacy, University of Pisa, 56126 Pisa, Italy. Electronic address: lamendola@farm.unipi.it.
authors.forename: Diego
authors.initials: D
authors.lastname: La Mendola
authors.affiliation: Institute of Biostructures and Bioimages, National Council of Research (CNR), Viale Andrea Doria, 6, I-95125 Catania, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Rizzarelli
authors.affiliation: Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
mesh_terms: D003300:Copper / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D012335:RNA, Ribosomal / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D012335:RNA, Ribosomal; C088179:RNA, ribosomal, 45S; D003300:Copper; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
keywords: ALS; Angiogenesis; Angiogenin; Copper; Human endothelial cells