Apoptosis Induced by Src-Family Tyrosine Kinase Inhibitors in Cultured Rat Cortical Cells
| Autor: | Tsuneo Takadera, Mineki Fujibayashi, Satoru Kato, Yoshiki Koriyama |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Programmed cell death
Indoles MAP Kinase Signaling System Apoptosis SRC Family Tyrosine Kinase Toxicology Maleimides Focal adhesion Glycogen Synthase Kinase 3 chemistry.chemical_compound Pregnancy Animals Src family kinase Enzyme Inhibitors Insulin-Like Growth Factor I Rats Wistar Cells Cultured Cerebral Cortex Neurons Sulfonamides Caspase 3 Chemistry Akt/PKB signaling pathway General Neuroscience Benzazepines Caspase 9 Rats Cell biology Neuroprotective Agents Pyrimidines src-Family Kinases SU6656 Focal Adhesion Protein-Tyrosine Kinases Cancer research Female Proto-Oncogene Proteins c-akt Tyrosine kinase Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Neurotoxicity Research. 21:309-316 |
| ISSN: | 1476-3524 1029-8428 |
| Popis: | In the central nervous system, members of the Src family of tyrosine kinases (SFKs) are widely expressed and are abundant in neurons. The purpose of this study is to examine whether glycogen synthase-3 (GSK-3) is involved in SFK inhibitor-induced apoptosis. PP2 and SU6656, SFK inhibitors, increased apoptotic cell death with morphological changes that were characterized by cell shrinkage, chromatin condensation, or nuclear fragmentation. Moreover, both activation of caspase-9 and caspase-3 were accompanied by the cell death. GSK-3 inhibitors, such as alsterpaullone and SB216763, prevented the PP2-induced apoptosis. In addition, insulin-like growth factor-I prevented the PP2-induced cell death and PP2 inhibited phosphorylation of focal adhesion kinase (FAK). Phosphorylation of FAK on Tyr 576 by Src activates FAK. These results suggest that inhibition of SFK induces apoptosis possibly via blocking of FAK/phosphatidylinositol-3 kinase/Akt signaling pathway and activation of GSK-3 is involved in the cell death in rat cortical neurons. |
| Databáze: | OpenAIRE |
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