title: Role of adenosine in the hypoxic induction of vascular endothelial growth factor in porcine brain derived microvascular endothelial cells.
abstract: Hypoxia induced the mRNA expression of vascular endothelial growth factor (VEGF) in porcine brain derived microvascular endothelial cells (BMEC) in a time-dependent manner. Corresponding to the mRNA induction the protein level of VEGF was elevated during hypoxia. The adenosine A1 receptor antagonist 8-phenyltheophylline (8-PT) reduced the hypoxia-induced VEGF mRNA and protein expression significantly. The treatment of BMEC with cobalt chloride-known to activate an oxygen sensing mechanism similar to the one used by the erythropoietin gene-also induced the VEGF mRNA expression, but 8-PT did not reduce this VEGF induction. Although, earlier studies revealed that agents like phorbolester induced the VEGF mRNA expression, the specific inhibitor of the proteinkinase C (PKC) bisindolylmaleimide (BIM) did not reduce but enhanced the hypoxia-induced VEGF mRNA expression. These results indicate that the VEGF induction in BMEC can proceed through PKC-dependent and -independent pathways (like those acting via the putative oxygen sensor). Hypoxia in BMEC probably activates the PKC-dependent pathway mainly via adenosine which might be formed during hypoxia and thereby inhibits activation of PKC-independent, oxygen sensing, pathways. This suggestion was supported by the fact that hypoxia as well as adenosine increased the VEGF mRNA expression post-transcriptionally by enhancing the stability of the VEGF mRNA [corrected].
authors.affiliation: Max-Planck Institute for Physiological and Clinical Research, Bad Nauheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Fischer
authors.forename: R
authors.initials: R
authors.lastname: Knöll
authors.forename: D
authors.initials: D
authors.lastname: Renz
authors.forename: G F
authors.initials: GF
authors.lastname: Karliczek
authors.forename: W
authors.initials: W
authors.lastname: Schaper
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000166:cytology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D014176:Protein Biosynthesis / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger / Q000235:genetics; D013552:Swine; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: 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; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine