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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Brain-Derived Neurotrophic Factor / pharmacology*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Differentiation / drug effects
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Cell Survival / drug effects
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Cell Survival / physiology
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Chromones / pharmacology
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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Humans
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases*
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Morpholines / pharmacology
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Nerve Growth Factors / pharmacology*
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Neurites / drug effects
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Neurites / physiology*
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Neuroblastoma
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Neuroprotective Agents / pharmacology
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Neurotrophin 3
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Phosphatidylinositol 3-Kinases / metabolism*
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Proto-Oncogene Proteins / genetics
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor, Ciliary Neurotrophic Factor
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Receptor, trkA
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Receptor, trkC
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Receptors, Nerve Growth Factor / genetics
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Recombinant Proteins / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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Tretinoin / pharmacology
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Tumor Cells, Cultured
Substances
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Brain-Derived Neurotrophic Factor
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Chromones
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Enzyme Inhibitors
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Flavonoids
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Morpholines
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Nerve Growth Factors
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Neuroprotective Agents
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Neurotrophin 3
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Proto-Oncogene Proteins
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Receptor, Ciliary Neurotrophic Factor
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Receptors, Nerve Growth Factor
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Recombinant Proteins
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neurotrophin 5
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Tretinoin
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Phosphatidylinositol 3-Kinases
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Receptor Protein-Tyrosine Kinases
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Receptor, trkA
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Receptor, trkC
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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neurotrophin 4
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one