Insulin-like growth factor-1 provides protection against psychosine-induced apoptosis in cultured mouse oligodendrocyte progenitor cells using primarily the PI3K/Akt pathway
| Autor: | Han Zhi Rao, Mariam Zaka, David A. Wenger, Paola Luzi, Mohammad A. Rafi |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Programmed cell death
MAP Kinase Signaling System medicine.medical_treatment Apoptosis Receptor IGF Type 1 Mice Phosphatidylinositol 3-Kinases Cellular and Molecular Neuroscience Insulin-like growth factor medicine Animals Insulin-Like Growth Factor I Phosphorylation Progenitor cell Extracellular Signal-Regulated MAP Kinases Molecular Biology Protein kinase B Cells Cultured PI3K/AKT/mTOR pathway Dose-Response Relationship Drug biology Galactocerebrosidase Stem Cells Psychosine Cell Biology Leukodystrophy Globoid Cell Cell biology Mice Inbred C57BL Oligodendroglia Insulin receptor Biochemistry biology.protein Proto-Oncogene Proteins c-akt |
| Zdroj: | Molecular and Cellular Neuroscience. 30:398-407 |
| ISSN: | 1044-7431 |
| Popis: | Psychosine (galactosylsphingosine) is a toxic metabolite that accumulates in globoid cell leukodystrophy (GLD) due to the deficiency of galactocerebrosidase (GALC) activity. This results in subsequent programmed cell death of oligodendrocytes and demyelination in human patients and animal models. We investigated the potential role of insulin-like growth factor-1 (IGF-1) in modifying the apoptotic effect of psychosine in cultured mouse oligodendrocyte progenitor cells (OLP-II). We show that psychosine inhibits the phosphorylation of Akt and Erk1/Erk2 (Erk1/2), which are the main anti-apoptotic pathways of the IGF-1 receptor (IGF-1R). Although IGF-1 sustained phosphorylation of both of these pathways, it provided maximum protection to OLP-II cells from psychosine-induced cell death in a PI3K/Akt-dependent manner. The effects of IGF-1 were dose-dependent and resulted in increased IGF-1R autophosphorylation levels. Although relatively high concentrations of IGF-1 also resulted in the activation of the insulin receptor (IR), its effect was more significant on the IGF-1R. |
| Databáze: | OpenAIRE |
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