Transient signaling of Erk1/2, Akt and PLCgamma induced by nerve growth factor in brain capillary endothelial cells.
Cumulative evidences suggest that nerve growth factor (NGF) promotes angiogenic effects such as proliferation and migration of endothelial cells (ECs) from different vascular beds, induces capillary sprouting in chorioallantoic membrane and improves in vivo vascularization in a hind-limb ischemic model. In the present study, we sought to investigate the signaling properties of NGF in a microcapillary ECs model compared to those of a neuronal model. NGF-induced phosphorylation of signaling molecules Erk1/2, Akt and PLCgamma were measured using Western blotting and compared between mouse NGF (mNGF) and snake venom NGF analogues. NGFs-induced signaling was TrkA mediated as evident by inhibition with the TrkA antagonist K252a. NGF and its analogues-induced signaling in ECs were characterized by a transient effect in contrast to a prolonged stimulation in neuronal cells. The potency of mouse, cobra and viper NGFs to induce Erk1/2 phosphorylation in ECs was higher than in neurons. In ECs, mNGF exhibited the highest efficacy of stimulation of Erk1/2 phosphorylation, followed by viper and cobra NGFs. The efficacy of stimulation of Erk1/2 phosphorylation measured with neurons was opposite from that in ECs. NGF-induced temporal signaling differences between ECs and neurons may explain the dual vascular and neurotrophic effects of this growth factor.
Lecht
Shimon
S
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Arien-Zakay
Hadar
H
Wagenstein
Yoav
Y
Inoue
Seiji
S
Marcinkiewicz
Cezary
C
Lelkes
Peter I
PI
Lazarovici
Philip
P
D000818:Animals; D001921:Brain / Q000098:blood supply*; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D049033:Chorioallantoic Membrane / Q000378:metabolism; D004546:Elapid Venoms / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D026121:Indole Alkaloids / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014757:Viper Venoms / Q000494:pharmacology
D002227:Carbazoles; D004546:Elapid Venoms; D026121:Indole Alkaloids; D014757:Viper Venoms; D020932:Nerve Growth Factor; C049985:staurosporine aglycone; D020917:Receptor, trkA; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D051966:Phospholipase C gamma