Adenosine as an endogenous mediator of hypoxia for induction of vascular endothelial growth factor mRNA in U-937 cells.
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-(beta-hydroxyethyl)theophylline, 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.
Hashimoto
E
E
Fourth Department of Internal Medicine, Tokyo University Branch Hospital, Japan.
Kage
K
K
Ogita
T
T
Nakaoka
T
T
Matsuoka
R
R
Kira
Y
Y
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D001483:Base Sequence; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D015687:Cell Hypoxia; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017931:DNA Primers; D016228:Endothelial Growth Factors; D008222:Lymphokines; D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019830:Adenosine-5'-(N-ethylcarboxamide); C057837:3,7-dimethyl-1-propargylxanthine; D003994:Bucladesine; D000243:Adenosine Deaminase; D000241:Adenosine; D013805:Theobromine