Involvement of caspase-2 activation in aurora kinase inhibitor-induced cell death in axin-expressing L929 cells
| Autor: | Jee Hye Shin, Shi Mun Kim, Sewon Kim, Eun Jin Choi, Ki Joon Song, Sun Ho Kee |
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| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Programmed cell death Poly ADP ribose polymerase Clinical Biochemistry Poly (ADP-Ribose) Polymerase-1 Pharmaceutical Science macromolecular substances Cell fate determination urologic and male genital diseases Cell Line Cell membrane Mice Necrosis Aurora kinase Axin Protein GSK-3 Aurora Kinases medicine Animals Pharmacology Caspase 8 Cell Death Chemistry Biochemistry (medical) Wnt signaling pathway Caspase 2 Cell Biology Caspase Inhibitors female genital diseases and pregnancy complications Cell biology Enzyme Activation medicine.anatomical_structure Apoptosis Poly(ADP-ribose) Polymerases |
| Zdroj: | Apoptosis : an international journal on programmed cell death. 19(4) |
| ISSN: | 1573-675X |
| Popis: | Axin is a multifunctional protein that participates in many cellular events including Wnt signaling and cell fate determination. Aurora kinase inhibitor (AKI)-induced cell death and cell membrane rupture is facilitated in L929 cells expressing axin (L-axin cells) through the activation of poly ADP-ribose polymerase (PARP). We observed that caspase-2 activity is required for AKI-induced cell death. Inhibition of caspase-2 activity suppressed AKI-induced PARP activation and mitochondrial dysfunction, resulting in a decrease in AKI-induced cell death. When an axin mutant deleted for the glycogen synthase kinase 3β (GSK3β)-binding domain was expressed in L929 cells (L-ΔGSK cells), AKI-induced caspase-2 activation and cell death decreased. AKI treatment reduced the expression of a 32-kDa caspase-2 splicing variant (caspase-2S) in most L-axin cells, but not in L-ΔGSK cells. These results suggest that AKI-induced caspase-2 activation in L-axin cells might be due to a decrease in the expression of caspase-2S, which inhibits caspase-2 activity. In addition, AKI treatment failed to activate caspase-8 and treatment with necrostatin inhibited AKI-induced cell death in L-axin cells, suggesting that the absence of caspase-8 activation might favor necrotic cell death. Axin expression may facilitate AKI-induced caspase-2 activation followed by activation of PARP and initiation of the necrotic cell death pathway. |
| Databáze: | OpenAIRE |
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