The Ionophoric Activity of a Pro-Apoptotic VEGF165 Fragment on HUVEC Cells

International Journal of Molecular Sciences

MariannaF. Tomasello¹  MicheleF. M. Sciacca¹  Stefania Zimbone¹  Sara García-Viñuales¹  Danilo Milardi¹  Giulia Grasso¹  AnnaM. Santoro¹  Claudia Martini²  MariaL. Trincavelli²  Diego La Mendola²  Chiara Giacomelli² 

[1] CNR Istituto di Cristallografia Sede Secondaria di Catania, Via Gaifami 18, 95126 Catania, Italy;Dipartimento di Farmacia, Università di Pisa, Via Bonanno Pisano 6, 56126 Pisa, Italy;

关键词: copper;    peptides;    vascular endothelial growth factor;    ionophore;    HUVEC;    apoptosis;   

DOI  :  10.3390/ijms21082866

来源: DOAJ

【 摘 要 】

Copper plays an important role as a regulator in many pathologies involving the angiogenesis process. In cancerogenesis, tumor progression, and angiogenic diseases, copper homeostasis is altered. Although many details in the pathways involved are still unknown, some copper-specific ligands have been successfully used as therapeutic agents. Copper-binding peptides able to modulate angiogenesis represent a possible way to value new drugs. We previously reported that a fragment (VEGF73-101) of vascular endothelial growth factor (VEGF165), a potent angiogenic, induced an apoptotic effect on human umbilical vein endothelial cells. The aim of this study was to investigate the putative copper ionophoric activity of VEGF73-101, as well as establish a relationship between the structure of the peptide fragment and the cytotoxic activity in the presence of copper(II) ions. Here, we studied the stoichiometry and the conformation of the VEGF73-101/Cu(II) complexes and some of its mutated peptides by electrospray ionization mass spectrometry and circular dichroism spectroscopy. Furthermore, we evaluated the effect of all peptides in the absence and presence of copper ions by cell viability and cytofuorimetric assays. The obtained results suggest that VEGF73-101 could be considered an interesting candidate in the development of new molecules with ionophoric properties as agents in antiangiogenic therapeutic approaches.

【 授权许可】

Unknown