Intracellular events mediating insulin-like growth factor I-induced oligodendrocyte development: modulation by cyclic AMP.
Insulin-like growth factor I (IGF-I) is a potent inducer of oligodendrocyte development and myelination. Although IGF-I intracellular signaling has been well described in several cell types, intracellular mechanisms for IGF-I-induced oligodendrocyte development have not been defined. By using specific inhibitors of intracellular signaling pathways, we report here that the MAPK and phosphatidylinositol 3-kinase signaling pathways are required for the full effect of IGF-I on oligodendrocyte development in primary mixed rat cerebrocortical cell cultures. The MAPK activation, but not the phosphatidylinositol 3-kinase activation, leads to phosphorylation of the cAMP response element-binding protein, which is necessary for IGF-I to induce oligodendrocyte development. cAMP, although it does not show any effect on oligodendrocyte development, has an inhibitory effect on IGF-I-induced oligodendrocyte development that is mediated by the cAMP-dependent protein kinase. Furthermore, cAMP also has an inhibitory effect on IGF-I-dependent MAPK activation. This is a cAMP-dependent protein kinase-independent effect and probably contributes to the cAMP action on IGF-I-induced oligodendrocyte development.
Palacios
Nuria
N
Servicio de Endocrinología, Hospital Ramón y Cajal, Madrid, Spain.
Sánchez-Franco
Franco
F
Fernández
Miriam
M
Sánchez
Isabel
I
Cacicedo
Lucinda
L
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology; D000242:Cyclic AMP / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects*; D008954:Models, Biological; D004676:Myelin Basic Protein / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D014404:Tubulin; D007334:Insulin-Like Growth Factor I; D000242:Cyclic AMP; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases