Neurogenin 1 Mediates Erythropoietin Enhanced Differentiation of Adult Neural Progenitor Cells
| Autor: | Ying Wang, Rui L Zhang, Michael Chopp, Zhong X Jiao, Sara R Gregg, Lei Wang, Yvonne LeTourneau, Zheng G Zhang |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Neurite Cellular differentiation Subventricular zone Nerve Tissue Proteins Biology Phosphatidylinositol 3-Kinases Basic Helix-Loop-Helix Transcription Factors Neurites medicine Animals Rats Wistar Progenitor cell Erythropoietin Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Neurons Stem Cells Neurogenesis Cell Differentiation Recombinant Proteins Neural stem cell Rats Cell biology medicine.anatomical_structure Neurology Neurology (clinical) Cardiology and Cardiovascular Medicine Proto-Oncogene Proteins c-akt Neuroscience Transcription Factors |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 26:556-564 |
| ISSN: | 1559-7016 0271-678X |
| Popis: | Proneuronal basic helix–loop–helix (bHLH) transcription factor, neurogenin 1 (Ngn1), regulates neuronal differentiation during development of the cerebral cortex. Akt mediates proneuronal bHLH protein function to promote neuronal differentiation. Here, we show that recombinant human erythropoietin (rhEPO) significantly increased Akt activity and Ngn1 mRNA levels in neural progenitor cells derived from the subventricular zone (SVZ) of adult rat, which was coincident with increases of neural progenitor cell proliferation, differentiation, and neurite outgrowth. Inhibition of Akt activity by the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) inhibitor, LY294002, abolished rhEPO-increased Ngn1 mRNA levels and the effects of rhEPO on neural progenitor cells. In addition, reducing expression of endogenous Ngn1 by means of short-interfering RNA (siRNA) blocked rhEPO-enhanced neuronal differentiation and neurite outgrowth but not rhEPO-increased proliferation. Furthermore, treatment of stroke rat with rhEPO significantly increased Ngn1 mRNA levels in SVZ cells. These data suggest that rhEPO acts as an extracellular molecule that activates the PI3K/Akt pathway, which enhances adult neural progenitor cell proliferation, differentiation, and neurite outgrowth, and Ngn1 is required for Akt-mediated neuronal differentiation and neurite outgrowth. |
| Databáze: | OpenAIRE |
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