Analysis of the NF-κB and PI 3-Kinase/Akt Survival Pathways in Nerve Growth Factor-Dependent Neurons
| Autor: | Patrick D. Sarmiere, Robert S. Freeman |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Programmed cell death
Cell Survival Proto-Oncogene Proteins c-jun Cytochrome c Group Protein Serine-Threonine Kinases Biology Phosphatidylinositol 3-Kinases Cellular and Molecular Neuroscience chemistry.chemical_compound NF-KappaB Inhibitor alpha Proto-Oncogene Proteins Nerve Growth Factor Animals Phosphatidylinositol Phosphorylation Molecular Biology Protein kinase B Cells Cultured Phosphoinositide-3 Kinase Inhibitors Neurons Cell Death Kinase Cytochrome c NF-kappa B NF-κB Cell Biology Embryo Mammalian Proto-Oncogene Proteins c-rel Mitochondria Rats Cell biology DNA-Binding Proteins Nerve growth factor nervous system chemistry Cancer research biology.protein I-kappa B Proteins Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Molecular and Cellular Neuroscience. 18:320-331 |
| ISSN: | 1044-7431 |
| DOI: | 10.1006/mcne.2001.1021 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect