Extracellular-Regulated Kinases and Phosphatidylinositol 3-Kinase Are
Involved in Brain-Derived Neurotrophic Factor-Mediated Survival and
neuritogenesis of the Neuroblastoma Cell Line SH-SY5Y |
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Authors: | M Encinas M Iglesias N Llecha & J X Comella |
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Institution: | Department de Ciències Mèdiques Bàsiques, Facultat de Medicina, Universitat de Lleida, Catalonia, Spain. |
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Abstract: | Retinoic acid (RA) induces the differentiation of many cell lines, including those derived from neuroblastoma. RA treatment of SH-SY5Y cells induces the appearance of functional Trk B and Trk C receptors. Acute stimulation of RA-predifferentiated SH-SY5Y cells with brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), or neurotrophin 4/5 (NT-4/5), but not nerve growth factor (NGF), induces Trk autophosphorylation, followed by phosphorylation of Akt and the extracellular signal-regulated kinases (ERKs) 1 and 2. In addition, BDNF, NT-3, or NT-4/5, but not NGF, promotes cell survival and neurite outgrowth in serum-free medium. The mitogen-activated protein kinase and ERK kinase (MEK) inhibitor PD98059 blocks BDNF-induced neurite outgrowth and growth-associated protein-43 expression but has no effects on cell survival. On the other hand, the phosphatidylinositol 3-kinase inhibitor LY249002 reverses the survival response elicited by BDNF, leading to a cell death with morphological features of apoptosis. |
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Keywords: | Trk Neurotrophin Neuroblastoma Neurodegeneration |
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