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Title: Analysis of the NF-kappa B and PI 3-kinase/Akt survival pathways in nerve growth factor-dependent neurons.

Authors: Sarmiere, P D; Freeman, R S

Published In Mol Cell Neurosci, (2001 Sep)

Abstract: Nerve growth factor (NGF) readdition to NGF-deprived neurons can halt Jun N-terminal kinase (JNK) activation, cytochrome c release, and cell death through mechanisms that may involve phosphatidylinositol (PI) 3-kinase, Akt, and nuclear factor kappa B (NF-kappaB). We found that expression of the NF-kappaB protein c-Rel in NGF-deprived neurons blocks cytochrome c release but does not inhibit c-Jun phosphorylation. Conversely, inhibition of NF-kappaB in NGF-maintained neurons promotes cytochrome c release and cell death. In contrast to c-Rel, activated PI 3-kinase and Akt inhibit c-Jun phosphorylation but have only a small effect on cytochrome c release. Finally, although c-Rel can protect neurons from death caused by inhibitors of PI 3-kinase or Akt, NF-kappaB function is not critical for Akt-promoted survival. These results suggest that the PI 3-kinase/Akt and NF-kappaB survival pathways target distinct cell death events in neurons.

PubMed ID: 11591132 Exiting the NIEHS site

MeSH Terms: Animals; Cell Death/drug effects; Cell Death/physiology; Cell Survival/drug effects; Cell Survival/genetics; Cell Survival/physiology; Cells, Cultured; Cytochrome c Group/metabolism; Cytochrome c Group/secretion; DNA-Binding Proteins/biosynthesis; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Embryo, Mammalian; I-kappa B Proteins*; Mitochondria/enzymology; Mitochondria/genetics; Mitochondria/secretion; NF-kappa B/antagonists & inhibitors; NF-kappa B/physiology*; Nerve Growth Factor/deficiency; Nerve Growth Factor/physiology*; Neurons/metabolism; Neurons/physiology*; Phosphatidylinositol 3-Kinases/antagonists & inhibitors; Phosphatidylinositol 3-Kinases/biosynthesis; Phosphatidylinositol 3-Kinases/physiology*; Phosphorylation; Protein-Serine-Threonine Kinases*; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-jun/antagonists & inhibitors; Proto-Oncogene Proteins c-jun/metabolism; Proto-Oncogene Proteins c-rel/biosynthesis; Proto-Oncogene Proteins c-rel/physiology; Proto-Oncogene Proteins/antagonists & inhibitors; Proto-Oncogene Proteins/biosynthesis; Proto-Oncogene Proteins/physiology*; Rats; Signal Transduction/drug effects; Signal Transduction/physiology*

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