Angiopoietin-1 promotes neurite outgrowth from dorsal root ganglion cells positive for Tie-2 receptor.
The effects of vascular factors on the nervous system are still poorly investigated. Angiopoietin-1 (Ang-1), an endothelial cell growth factor with influences on blood vessel stabilization, has been recently reported to prevent apoptosis in a neuroblastoma cell line via a pathway dependent on Tie-2 receptor. The present study focuses on the effect of Ang-1 on cultured dorsal root ganglion (DRG) cells isolated from 1-day-old rats. Three-day-old DRG cultures were exposed to Ang-1 treatment under serum-free condition for another 5 days and stained with antibodies against neurofilament (NF) 200 protein. Neurite length and density increased compared with those of controls. Double-immunofluorescence staining demonstrated the co-localization of the Tie-2 receptor in some NF-200-positive perikarya. The reverse transcription/polymerase chain reaction technique identified Tie-2 receptor mRNA in intact DRG and in Ang-1-stimulated DRG cell cultures, but not in a Schwann cell line or in primary astrocyte cultures. Western blotting confirmed that the expression of NF 68 protein in cultures treated with Ang-1 or nerve growth factor was higher than that in cultures treated with medium alone. When the Tie-2 receptor was blocked with anti-Tie-2 receptor antibody, neurite outgrowth was severely impeded. Induction of trkA-receptor protein expression was observed to be dependent on the presence of Tie-2 receptors. We conclude that Ang-1 promotes neurite outgrowth from DRG cells positive for Tie-2 receptor. The signalling pathway appears to involve transactivation of the trkA receptor.
Kosacka
Joanna
J
Institute of Anatomy, University of Leipzig, Liebigstrasse 13, 04103, Leipzig, Germany.
Figiel
Maciej
M
Engele
Jürgen
J
Hilbig
Heidegard
H
Majewski
Mariusz
M
Spanel-Borowski
Katharina
K
D042683:Angiopoietin-1 / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D005727:Ganglia, Spinal / Q000166:cytology*; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011920:Rats, Inbred WF; D042787:Receptor, TIE-2 / Q000187:drug effects* / Q000378:metabolism; D020917:Receptor, trkA / Q000187:drug effects / Q000378:metabolism*
D042683:Angiopoietin-1; D016895:Culture Media, Serum-Free; D042787:Receptor, TIE-2; D020917:Receptor, trkA