Binding of ATP to vascular endothelial growth factor isoform VEGF-A165 is essential for inducing proliferation of human umbilical vein endothelial cells

Background: ATP binding is essential for the bioactivity of several growth factors including nerve growth factor, fibroblast growth factor-2 and brain-derived neurotrophic factor. Vascular endothelial growth factor isoform 165 (VEGF-A165) induces the proliferation of human umbilical vein endothelial...

Authors: Gast, Ronald E.
König, Simone
Rose, Karsten
Ferenz, Katja
Krieglstein, Josef
Division/Institute:FB 12: Chemie und Pharmazie
FB 05: Medizinische Fakultät
Document types:Article
Media types:Text
Publication date:2011
Date of publication on miami:12.02.2013
Modification date:16.04.2019
Edition statement:[Electronic ed.]
Source:BMC Biochemistry 12 (2011) 28
DDC Subject:570: Biowissenschaften; Biologie
License:CC BY 2.0
Language:English
Notes:Finanziert durch den Open-Access-Publikationsfonds 2011/2012 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
URN:urn:nbn:de:hbz:6-67389483208
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-67389483208
Other Identifiers:DOI: doi:10.1186/1471-2091-12-28
Digital documents:1471-2091-12-28.pdf

Background: ATP binding is essential for the bioactivity of several growth factors including nerve growth factor, fibroblast growth factor-2 and brain-derived neurotrophic factor. Vascular endothelial growth factor isoform 165 (VEGF-A165) induces the proliferation of human umbilical vein endothelial cells, however a dependence on ATPbinding is currently unknown. The aim of the present study was to determine if ATP binding is essential for the bioactivity of VEGF-A165. Results: We found evidence that ATP binding toVEGF-A165 induced a conformational change in the secondary structure of the growth factor. This binding appears to be significant at the biological level, as we found evidence that nanomolar levels of ATP (4-8 nm) are required for the VEGF-A165-induced proliferation of human umbilical vein endothelial cells. At these levels, purinergic signaling by ATP via P2 receptors can be excluded. Addition of alkaline phosphate to cell culture lowered the ATP concentration in the cell culture medium to 1.8 nM and inhibited cell proliferation. Conclusions: We propose that proliferation of endothelial cells is induced by a VEGF-A165-ATP complex, rather than VEGF-A165 alone.