Abstract
Our previous study demonstrated that huperzine A, a selective acetylcholinesterase inhibitor, stimulates the synthesis of nerve growth factor (NGF) in cultured rat cortical astrocytes. The present studies are designed to examine if huperzine A exerts its neuroprotective activity against oxidative stress damage through increasing the synthesis of NGF in SHSY5Y neuroblastoma cells. Transient exposure of the cells to 200 microM H2O2 triggered a significant reduction of cell viability and decreased the mRNA and protein levels of NGF, neurotrophin receptor P75 (P75NTR) receptor and tyrosine kinase A (TrkA) receptor. Incubation of cells with 10 microM huperzine A prior to H2O2 exposure significantly elevated their survival and restored the mRNA and protein levels of NGF, P75NTR receptor and TrkA receptor. These neuroprotective effects of huperzine A on H2O2-induced cytotoxicity were blocked by the TrkA receptor phosphorylation inhibitor K252alpha, and were antagonized by the mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) inhibitor, PD98059. The present results indicate that the cytoprotective effect of huperzine A is mediated at least partly by up-regulated NGF and NGF receptors. The results also show that the MAP/ERK kinase signal pathway is crucial for huperzine A to protect against H2O2-induced damage in SHSY5Y cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids
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Androstadienes / pharmacology
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Blotting, Western
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Carbazoles / pharmacology
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Cell Line, Tumor
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Cell Survival / drug effects
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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Humans
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Hydrogen Peroxide / pharmacology
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Immunohistochemistry
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Indole Alkaloids
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Nerve Growth Factor / genetics*
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Nerve Growth Factor / metabolism
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Neuroblastoma / genetics
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Neuroblastoma / metabolism
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Neuroblastoma / pathology
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Neuroprotective Agents / pharmacology
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Oxidants / pharmacology
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Oxidative Stress / drug effects*
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Protein Kinase Inhibitors / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptor, Nerve Growth Factor
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Receptor, trkA / genetics
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Receptor, trkA / metabolism
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Receptors, Nerve Growth Factor / genetics
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Receptors, Nerve Growth Factor / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sesquiterpenes / pharmacology*
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Wortmannin
Substances
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Alkaloids
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Androstadienes
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Carbazoles
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Enzyme Inhibitors
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Flavonoids
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Indole Alkaloids
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Neuroprotective Agents
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Oxidants
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Protein Kinase Inhibitors
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RNA, Messenger
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Receptor, Nerve Growth Factor
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Receptors, Nerve Growth Factor
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Sesquiterpenes
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huperzine A
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Nerve Growth Factor
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staurosporine aglycone
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Hydrogen Peroxide
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Receptor, trkA
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Calcium-Calmodulin-Dependent Protein Kinases
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Wortmannin