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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 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.

Titel: Binding of ATP to vascular endothelial growth factor isoform VEGF-A165 is essential for inducing proliferation of human umbilical vein endothelial cells
Verfasser: Gast, Ronald E.
König, Simone
Rose, Karsten
Ferenz, Katja GND
Krieglstein, Josef GND
Organisation: FB 12: Chemie und Pharmazie
FB 05: Medizinische Fakultät
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 27.05.2011
Publikation in MIAMI: 12.02.2013
Datum der letzten Änderung: 18.08.2014
Quelle: BMC Biochemistry 12 (2011) 28
Fachgebiete: Biowissenschaften; Biologie
Lizenz: CC BY 2.0
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2011/2012 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-67389483208
Permalink: http://nbn-resolving.de/urn:nbn:de:hbz:6-67389483208
DOI: doi:10.1186/1471-2091-12-28
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