Abstract
The signaling pathways that mediate the ability of NGF to support survival of dependent neurons are not yet completely clear. However previous work has shown that the c-Jun pathway is activated after NGF withdrawal, and blocking this pathway blocks neuronal cell death. In this paper we show that over-expression in sympathetic neurons of phosphatidylinositol (PI) 3-kinase or its downstream effector Akt kinase blocks cell death after NGF withdrawal, in spite of the fact that the c-Jun pathway is activated. Yet, neither the PI 3-kinase inhibitor LY294002 nor a dominant negative PI 3-kinase cause sympathetic neurons to die if they are maintained in NGF. Thus, although NGF may regulate multiple pathways involved in neuronal survival, stimulation of the PI 3-kinase pathway is sufficient to allow cells to survive in the absence of this factor.
MeSH terms
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Animals
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Cell Death / drug effects
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Cell Survival / drug effects
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Enzyme Activation
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Nerve Growth Factors / deficiency
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Nerve Growth Factors / physiology
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Neurons / drug effects
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Neurons / enzymology*
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Neurons / physiology*
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphatidylinositol 3-Kinases / physiology
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Phosphoinositide-3 Kinase Inhibitors
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Protein Serine-Threonine Kinases*
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Protein-Tyrosine Kinases / metabolism*
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Protein-Tyrosine Kinases / physiology
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-jun / biosynthesis
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Proto-Oncogene Proteins c-jun / metabolism
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Rats
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Superior Cervical Ganglion / drug effects
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Superior Cervical Ganglion / enzymology*
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Superior Cervical Ganglion / physiology*
Substances
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Nerve Growth Factors
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Phosphoinositide-3 Kinase Inhibitors
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-jun
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Protein-Tyrosine Kinases
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Akt1 protein, rat
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt