The same cellular signaling pathways mediate survival in sensory neurons that switch their trophic requirements during development.
A distinct subpopulation of rat dorsal root sensory (DRG) neurons, termed P-neurons, switch their trophic requirements for survival during development from nerve growth factor (NGF) at embryonic stages to basic fibroblast growth factor (bFGF) just after birth. We investigated in cultured P-neurons the intracellular signaling pathways mediating survival before and after this switch. The NGF-induced survival was completely blocked by either wortmannin (100 nM) or PD98059 (25-50 nM), which selectively inhibit the phosphatidylinositol 3-kinase-AKT (PI3 kinase-AKT) and mitogen-activated kinase kinase extracellular regulated kinase (MEK-ERKs) pathways, respectively. NGF activated AKT and ERKs in single embryonic P-neurons, as assayed by immunofluorescence of phosphorylated proteins. In concordance with the survival assays, wortmannin and PD98059 blocked AKT and ERKs activation, respectively. Following the trophic switch, bFGF used the same signaling pathways to promote survival of post-natal P-neurons, as either wortmannin or PD98059 blocked its effect. Also, bFGF activated AKT and ERKs in single P-neurons, and this activation was blocked by the same inhibitors. These results strongly suggest that both pathways concurrently mediate the action of NGF and bFGF during embryonic and post-natal periods, respectively. Thus, we report the novel result that the switch in trophic requirements occurs with conservation of the signaling pathways mediating survival.
Salvarezza
Susana B
SB
Cátedra de Biología Celular, Fac. Ciencias Exactas, Físicas y Naturales, UNC, Córdoba, Argentina.
López
Hector S
HS
Mascó
Daniel H
DH
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D029681:Arabidopsis Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000077191:Wortmannin
D000730:Androstadienes; D029681:Arabidopsis Proteins; D004791:Enzyme Inhibitors; D016222:Fibroblast Growth Factor 2; D005419:Flavonoids; D020928:Mitogen-Activated Protein Kinases; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015221:Potassium Channels; D000077191:Wortmannin; C074500:AKT1 protein, Arabidopsis; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one