Abstract
In the present study, we examined the effects of fluvoxamine on nerve growth factor (NGF)-induced neurite outgrowth inhibition by dexamethasone (DEX) in PC12 cells. Fluvoxamine increased NGF-induced neurite outgrowth. Compared with co-treatment with NGF and fluvoxamine, p-Akt levels were higher than the values without fluvoxamine. The phosphorylated extracellular regulated kinase 1/2 levels were slightly increased by co-treatment with NGF and fluvoxamine. Fluvoxamine concentration-dependently improved NGF-induced neurite outgrowth inhibition by DEX. Fluvoxamine also improved the decrease in the NGF-induced p-Akt level caused by DEX. Interestingly, the sigma-1 receptor antagonist NE-100 blocked the improvement effects of fluvoxamine on NGF-induced neurite outgrowth inhibition by DEX. The selective sigma-1 receptor agonist PRE-084 also improved NGF-induced neurite outgrowth inhibition by DEX, which is blocked by NE-100. These results indicate that the improvement effects of fluvoxamine on NGF-induced neurite outgrowth inhibition by DEX may be attributable to the phosphorylation of Akt and the sigma-1 receptor.
Keywords:
Nerve growth factor (NGF); dexamethasone (DEX); fluvoxamine; neurite outgrowth; phosphorylated Akt.
MeSH terms
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Animals
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Anisoles / pharmacology
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Anti-Anxiety Agents / pharmacology*
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Cell Differentiation / drug effects
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Dexamethasone / antagonists & inhibitors
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Dexamethasone / pharmacology
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Fluvoxamine / pharmacology*
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Gene Expression Regulation / drug effects*
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Glucocorticoids / antagonists & inhibitors
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Glucocorticoids / pharmacology
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / metabolism
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Morpholines / pharmacology
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Nerve Growth Factor / pharmacology
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Neuronal Outgrowth / drug effects*
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Neuronal Outgrowth / genetics
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Neurons / cytology
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Neurons / drug effects*
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Neurons / metabolism
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PC12 Cells
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Phosphorylation / drug effects
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Propylamines / pharmacology
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Proto-Oncogene Proteins c-akt / agonists
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / genetics*
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Proto-Oncogene Proteins c-akt / metabolism
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Rats
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Receptors, sigma / agonists
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Receptors, sigma / antagonists & inhibitors
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Receptors, sigma / genetics
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Receptors, sigma / metabolism
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Sigma-1 Receptor
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Signal Transduction
Substances
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Anisoles
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Anti-Anxiety Agents
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Glucocorticoids
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Morpholines
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Propylamines
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Receptors, sigma
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2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate
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N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride
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Dexamethasone
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Nerve Growth Factor
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Fluvoxamine