Induction of in vitro angiogenesis in the endothelial-derived cell line, EA hy926, by ethanol is mediated through PKC and MAPK.
We have previously shown that ethanol-induced injury to the gastric mucosa triggers increased expression of the angiogenic factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) and angiogenesis. To further investigate ethanol-induced angiogenesis, we used an in vitro angiogenesis model which employs the ability of an endothelial-derived cell line (EA hy926) to form tubelike structures resembling capillaries when plated on the matrix material, Matrigel. We report that serum-starved EA hy926 cells, incubated for as little as 5 minutes with ethanol concentrations of 1.0-2.5%, formed tubelike structures reflecting in vitro angiogenesis. Control cells, not incubated with ethanol, did not form tubelike structures. Incubation for 5 minutes with 2.5% ethanol resulted in increased activities of PKC and MAP kinase (ERK2) by 1.6-fold (p < 0.05) and 2.3-fold (P < 0.001), respectively. Furthermore, inhibitors of the MAPK kinase, MEK (PD98059) and PKC (GF 109203X) prevented the induction of in vitro angiogenesis by ethanol.
Jones
M K
MK
Department of Medicine, Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA.
Sarfeh
I J
IJ
Tarnawski
A S
AS
D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D048728:MAP Kinase Kinase Kinase 1; D008301:Maleimides / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007211:Indoles; D008301:Maleimides; D000431:Ethanol; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; C070515:bisindolylmaleimide I; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one