Neurotrophic Factors Prevent Ceramide-Induced Apoptosis Downstream of c-Jun N-Terminal Kinase Activation in PC12 Cells
| Autor: | Andrea J. Bilney, Perry J. Hartfield, Andrew W. Murray |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Programmed cell death
Ceramide Cell Survival Proto-Oncogene Proteins c-jun Morpholines Basic fibroblast growth factor Apoptosis Cysteine Proteinase Inhibitors Biology PC12 Cells Biochemistry Amino Acid Chloromethyl Ketones Cellular and Molecular Neuroscience chemistry.chemical_compound Sphingosine Neurotrophic factors Cyclic AMP Animals Hypoglycemic Agents Insulin Nerve Growth Factors Enzyme Inhibitors Flavonoids Neurons Protein Synthesis Inhibitors Epidermal Growth Factor Kinase Neuropeptides c-jun Thionucleotides Rats Androstadienes Enzyme Activation Cysteine Endopeptidases Neuroprotective Agents Nerve growth factor chemistry Chromones Cancer research Pituitary Adenylate Cyclase-Activating Polypeptide Fibroblast Growth Factor 2 Signal transduction Wortmannin |
| Zdroj: | Journal of Neurochemistry. 71:161-169 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1046/j.1471-4159.1998.71010161.x |
| Popis: | Neurotrophic factors prevent apoptosis of PC12 cells in serum-free medium. The present study determines whether neurotrophic factors can prevent ceramide-induced apoptosis in PC12 cells and investigates the role that c-Jun N-terminal kinase (JNK) activation may play in this system. Ceramide-induced apoptosis was inhibited by nerve growth factor, basic fibroblast growth factor, pituitary adenylyl cyclase-activating peptide, 4-(8-chlorophenylthio)cyclic AMP, and the caspase inhibitor benzyloxycarbonyl-Val-Ala-dl-Asp fluoromethyl ketone (zVAD-FMK). It was surprising that inhibition of extracellular signal-regulated kinase and/or phosphatidylinositol 3-kinase did not markedly block the protective effects exerted by neurotrophic factors against ceramide-induced apoptosis, suggesting that neurotrophic factors can promote survival independently of these signaling pathways. Treatment of PC12 cells with ceramide resulted in a time-dependent increase in JNK activity. However, neither neurotrophic factors nor zVAD-FMK attenuated ceramide-stimulated JNK activation. Further experiments indicated that ceramide-induced apoptosis in PC12 cells requires new protein synthesis, and that nerve growth factor and zVAD-FMK can prevent apoptosis after JNK activity has been detected. These results indicate that ceramide-induced JNK activation is an early event and may be required for the expression of essential components of the apoptotic machinery. It is anticipated that neurotrophic factors inhibit ceramide-induced apoptosis by affecting signaling events downstream of JNK activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text