Eintrag weiter verarbeiten
Netrin-1 induces angiogenesis via a DCC-dependent ERK1/2-eNOS feed-forward mechanism
Gespeichert in:
| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
|---|---|
| Personen und Körperschaften: | , |
| In: | Proceedings of the National Academy of Sciences, 103, 2006, 17, S. 6530-6535 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
|
| Schlagwörter: |
| Zusammenfassung: | <jats:p> Netrin-1 is critical for axonal pathfinding which shares similarities with formation of vascular network. Here we report that netrin-1 induction of angiogenesis is mediated by an increase in endothelial nitric oxide (NO <jats:sup>•</jats:sup> ) production, which occurs via a DCC-dependent, ERK1/2-eNOS feed-forward mechanism. Exposure of mature aortic endothelial cells to netrin-1 resulted in a potent, dose-dependent increase in NO <jats:sup>•</jats:sup> production, detected by electron spin resonance. Scavenging NO <jats:sup>•</jats:sup> with 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) abolished netrin-1 stimulated angiogenesis. Netrin-1-stimulated NO <jats:sup>•</jats:sup> production or angiogenesis was inhibited by DCC antibody, DCC small interfering RNA (siRNA), specific inhibitors (PD98059, U0126), or siRNAs for MEK1/2. PTIO attenuated ERK1/2 phosphorylation, indicating a feed-forward mechanism. Netrin-1 induced a time-dependent phosphorylation of eNOS <jats:sub>s1179, s116</jats:sub> and a rapid dephosphorylation of eNOS <jats:sub>t497</jats:sub> . Only eNOS <jats:sub>s1179</jats:sub> was sensitive to U0126 or PTIO. These data characterized a mechanism whereby netrin-1 promotes angiogenesis, which may broadly relate to cardiovascular, neuronal and cancer physiology. </jats:p> |
|---|---|
| Umfang: | 6530-6535 |
| ISSN: |
0027-8424
1091-6490 |
| DOI: | 10.1073/pnas.0511011103 |