Staurosporine-induced cell death in salmonid cells: the role of apoptotic volume decrease, ion fluxes and MAP kinase signaling
| Autor: | Muhammad Nawaz, Gerhard Krumschnabel, Claudia Manzl, Pablo J. Schwarzbaum, Tanja Maehr |
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| Rok vydání: | 2007 |
| Předmět: |
MAPK/ERK pathway
Cancer Research Programmed cell death 4-Acetamido-4'-isothiocyanatostilbene-2 2'-disulfonic Acid MAP Kinase Signaling System Clinical Biochemistry Pharmaceutical Science 4 4'-Diisothiocyanostilbene-2 2'-Disulfonic Acid Biology Membrane Potentials chemistry.chemical_compound Chlorides medicine Animals Staurosporine Enzyme Inhibitors Cells Cultured Cell Size Pharmacology Ion Transport Cell Death Kinase Biochemistry (medical) Cell Biology Transport inhibitor Quinidine Molecular biology Mitochondria Cell biology Enzyme Activation chemistry Apoptosis DIDS Oncorhynchus mykiss Mitogen-activated protein kinase Potassium biology.protein Mitogen-Activated Protein Kinases medicine.drug |
| Zdroj: | Apoptosis. 12:1755-1768 |
| ISSN: | 1573-675X 1360-8185 |
| Popis: | Apoptotic cell death in mammalian models is frequently associated with cell shrinkage. Inhibition of apoptotic volume decrease (AVD) is cytoprotective, suggesting that cell shrinkage is an important early event in apoptosis. In salmonid hepatoma and gill cells staurosporine induced apoptosis, as assessed by activation of effector caspases, nuclear condensation, and a decrease of mitochondrial membrane potential (MMP), and these changes were accompanied by cell shrinkage. The Cl- transport inhibitor DIDS and the K+ channel inhibitor quinidine prevented AVD, but only DIDS inhibited apoptosis. Other Cl- flux inhibitors, as well as a pan-caspase inhibitor, did not prevent cell shrinkage, but still prevented caspase activation. Furthermore, regulatory volume decrease (RVD) under hypotonic conditions was not facilitated, but diminished in apoptotic cells. Since all transport inhibitors used blocked RVD, but only DIDS and quinidine inhibited AVD, the ion transporters involved in both processes are apparently not identical. In addition, our data indicate that inhibition of Cl- fluxes rather than blocking cell shrinkage or K+ fluxes is important for preventing apoptosis. In line with this, inhibition of MAP kinases reduced RVD and not AVD, but still diminished caspase activation. Finally, we observed that MAP kinases were activated upon staurosporine treatment and that at least activation of ERK was prevented when AVD was inhibited. |
| Databáze: | OpenAIRE |
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