Adenosine as an Endogenous Mediator of Hypoxia for Induction of Vascular Endothelial Growth Factor mRNA in U-937 Cells

• Published in: Biochemical and biophysical research communications Vol. 204; no. 1; pp. 318 - 324
• Main Authors: Hashimoto, E., Kage, K., Ogita, T., Nakaoka, T., Matsuoka, R., Kira, Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.10.1994
• Subjects: Adenosine - analogs & derivatives; Adenosine - pharmacology; Adenosine - physiology; Adenosine Deaminase - pharmacology; Adenosine-5'-(N-ethylcarboxamide); Base Sequence; Blotting, Northern; Bucladesine - pharmacology; Cell Hypoxia; Cell Line; Cloning, Molecular; DNA Primers; Endothelial Growth Factors - biosynthesis; Gene Expression - drug effects; Humans; Lymphokines - biosynthesis; Molecular Sequence Data; Polymerase Chain Reaction - methods; Purinergic P1 Receptor Antagonists; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Theobromine - analogs & derivatives; Theobromine - pharmacology; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1994.2462

Adenosine induced by hypoxia exerts various effects via different types of receptors. Recently, hypoxia was shown to be a strong inducer of vascular endothelial growth factor, a secreted endothelial cell specific mitogen. In this report, we studied on effects of adenosine on inducibility of VEGF and possible mediation of hypoxia for its induction in U-937 cells. Hypoxia induced expression of VEGF mRNA with an early peak at 1 hour. 5′-N-ethylcarboxamidoadenosine, an adenosine analog, strongly induced VEGF mRNA, which was inhibited by 3,7-dimethyl-1-propargylxanthine (DMPX), an A2-antagonist. The hypoxic induction was inhibited by adenosine deaminase, 7-(β-hydroxyethyl)theophyline, a non-selective adenosine receptor antagonist and DMPX. These results suggest that the hypoxic induction of VEGF mRNA is mediated by adenosine via A2-receptor in U-937 cells.