Abstract
Nerve growth factor (NGF) induces persistent p42 and p44 mitogen-activated protein kinase (MAPK) activity in sympathetic neurones in parallel to its survival-promoting activity. To investigate whether these MAPK activities are necessary for NGF-induced survival, we have inhibited NGF-stimulated p42/p44 MAPK activity over extended periods using the compound 2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one (PD98059). Despite attaining up to 95% inhibition of p42/p44 MAPK activity in cultures treated with NGF and PD98059, neuronal survival is maintained undiminished, although a decrease in the density of the neuritic network is observed. Because p21Ras activity is essential for NGF-induced survival, we conclude that p21Ras-linked activities other than p42 and p44 MAPKs are responsible for mediating NGF-dependent survival of rat sympathetic neurones.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
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Cell Survival / drug effects
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Cells, Cultured
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Enzyme Inhibitors / pharmacology*
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Flavonoids / pharmacology*
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Kinetics
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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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Nerve Growth Factors / pharmacology*
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Neurites / drug effects
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Neurites / physiology
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Neurons / cytology
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Neurons / drug effects*
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Neurons / enzymology
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Rats
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Superior Cervical Ganglion / cytology
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Superior Cervical Ganglion / enzymology*
Substances
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Enzyme Inhibitors
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Flavonoids
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Nerve Growth Factors
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Protein-Tyrosine Kinases
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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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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one