Caspase activation in etoposide-treated fibroblasts is correlated to ERK phosphorylation and both events are blocked by polyamine depletion
| Autor: | Caroline A. Mackintosh, Claudio Marcello Caldarera, C. Clô, Claudio Stefanelli, Flavio Flamigni, Benedetta Tantini, Anthony E. Pegg, Carlo Guarnieri, Ivana Stanic, Carla Pignatti, Monia Fattori |
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| Rok vydání: | 2002 |
| Předmět: |
MAPK/ERK pathway
Eflornithine Biophysics Apoptosis Biochemistry c-Jun NH2-terminal kinase Ornithine decarboxylase Mice Coumarins Structural Biology Polyamines Putrescine Genetics medicine Animals Enzyme Inhibitors Phosphorylation Molecular Biology Caspase Etoposide Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 biology Kinase Cell Biology Fibroblasts Ornithine Decarboxylase Inhibitors Caspase Inhibitors Molecular biology Enzyme Activation Ornithine Decarboxylase Inhibitor Caspases biology.protein Extracellular signal-regulated kinase Mitogen-Activated Protein Kinases Signal transduction Oligopeptides Signal Transduction medicine.drug |
| Zdroj: | FEBS Letters. 527:223-228 |
| ISSN: | 0014-5793 |
| DOI: | 10.1016/s0014-5793(02)03242-8 |
| Popis: | Activation of the extracellular signal-regulated kinases (ERKs) 1 and 2 is correlated to cell survival, but in some cases ERKs can act in signal transduction pathways leading to apoptosis. Treatment of mouse fibroblasts with 20 microM etoposide elicited a sustained phosphorylation of ERK 1/2, that increased until 24 h from the treatment in parallel with caspase activity. The inhibitor of ERK activation PD98059 abolished caspase activation, but caspase inhibition did not reduce ERK 1/2 phosphorylation, suggesting that ERK activation is placed upstream of caspases. Both ERK and caspase activation were blocked in cells depleted of polyamines by the ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO). In etoposide-treated cells, DFMO also abolished phosphorylation of c-Jun NH(2)-terminal kinases triggered by the drug. Polyamine replenishment with exogenous putrescine restored the ability of the cells to undergo caspase activation and ERK 1/2 phosphorylation in response to etoposide. Ornithine decarboxylase activity decreased after etoposide, indicating that DFMO exerts its effect by depleting cellular polyamines before induction of apoptosis. These results reveal a role for polyamines in the transduction of the death signal triggered by etoposide. |
| Databáze: | OpenAIRE |
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