IGF-I and NT-3 signaling pathways in developing oligodendrocytes: differential regulation and activation of receptors and the downstream effector Akt.
A previous study from our laboratory demonstrated differences in the ability of insulin-like growth factor-I (IGF-I) and neurotrophin-3 (NT-3) to promote survival of pro-oligodendroblasts (pro-OLs) against glutamate-mediated apoptosis. In the current study, we tested whether submaximal concentrations of NT-3 would maintain receptor tyrosine kinase TrkC activation and Akt phosphorylation and thus promote long-term survival of the pro-OL against glutamate. Our results demonstrate that NT-3 at any concentration sufficient to activate the TrkC receptor results in a transient phosphorylation of the receptor and of Akt due, in part, to downregulation of the Trk receptor. In contrast, even submaximal IGF-I concentrations maintain long-term Akt activation and prevent glutamate-mediated apoptosis in pro-OLs. In addition, we also present data showing that IGF-I and NT-3 differentially activate their receptors and Akt depending on the maturational stage of the oligodendrocyte.
Ness
Jennifer K
JK
Department of Neuroscience and Anatomy, Penn State College of Medicine, Hershey, Pa 17033, USA.
Mitchell
Nina E
NE
Wood
Teresa L
TL
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000633:toxicity; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D020933:Neurotrophin 3 / Q000494:pharmacology*; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D011518:Proto-Oncogene Proteins; D018698:Glutamic Acid; D007334:Insulin-Like Growth Factor I; D020794:Receptor Protein-Tyrosine Kinases; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt