ing hypoxia. The adenosine A, receptor antagonist 8-phenyltheophylline (8-PT) reduced the hypoxia-induced VEGF mRNA and protein expression significantly.
ERRATUM Due 10 a printcrs error, part of the abstract of the paper below was missing in volume 5 , number 3 , pages 155--lhS and thcrcfore we are reprinting the correct version helow:
Role of Adenosine in the Hypoxic Induction of Vascular Endothelial Growth Factor in Porcine Brain Derived Microvascular Endothelial Cells
Endothelium Downloaded from informahealthcare.com by 223.84.10.205 on 05/20/14 For personal use only.
S. FISCHER:':. R. KNOLL, D. KENZ, G . F. KARLICZEK and W. SCHAPER
Hypoxia induced the mRNA expression of vascular endothelial growth factor (VEGF) in porcinc brain derived microvascular endothelial cells (BMEC) in a time-dependent manner. Corresponding to the mRNA induction thc protein level of VEGF was elevated during hypoxia. The adenosine A, 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, hut 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 HMEC 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 mHNA expression post-transcriptionally hy enhancing the stability of the VEGF mRNA. Kuyword.~: Adenosine. endothelial cclls. hypoxia; post-transcl.iptinna1 rcgulation, VEGF
