Ceramide-induced apoptosis of D283 medulloblastoma cells requires mitochondrial respiratory chain activity but occurs independently of caspases and is not sensitive to Bcl-xL overexpression
Autor: | Claus Reimertz, Monika Poppe, Jochen H. M. Prehn, Gudrun Münstermann, Donat Kögel |
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Rok vydání: | 2002 |
Předmět: |
Ceramide
Programmed cell death bcl-X Protein Apoptosis Bcl-xL Mitochondrion Ceramides Transfection DNA Mitochondrial Biochemistry Mitochondrial apoptosis-induced channel Electron Transport Electron Transport Complex IV Cellular and Molecular Neuroscience chemistry.chemical_compound Multienzyme Complexes Sphingosine Pyruvic Acid Tumor Cells Cultured Humans Enzyme Inhibitors Caspase Cell Death biology Calpain Electron Transport Complex II Molecular biology Chromatin Mitochondria Cell biology Enzyme Activation Succinate Dehydrogenase Glucose Mitochondrial respiratory chain Proto-Oncogene Proteins c-bcl-2 chemistry Caspases biology.protein Oxidoreductases Medulloblastoma |
Zdroj: | ResearcherID |
ISSN: | 1471-4159 0022-3042 |
DOI: | 10.1046/j.1471-4159.2002.01007.x |
Popis: | Ceramides are potent lipid second messengers that are involved in apoptotic and hypoxic/ischaemic neurone death. We investigated the role of mitochondria and the mitochondrial apoptosis pathway in ceramide-induced cell death using human D283 medulloblastoma cells with a reduced mitochondrial DNA copy number (rho- cells) and a corresponding defect in mitochondrial respiration. Treatment with the complex I inhibitor rotenone, C2- or C8-ceramide induced cell death in D283 control cells, while rho- cells were significantly protected. In contrast, activation of the mitochondrial apoptosis pathway by transient overexpression of the pro-apoptotic Bax protein or exposure to the kinase inhibitor staurosporine induced apoptosis to a similar extent in control and rho- cells. Overexpression of the antiapoptotic protein Bcl-xL failed to inhibit the toxic effect of C2-ceramide in D283 control cells, and no significant increase in caspase-3-like protease activity could be detected during the death process. Despite this, C2-ceramide induced significant chromatin condensation and cell shrinkage in D283 control cells, reminiscent of apoptosis. These morphological alterations were associated with the activation of calpains. Both apoptotic morphology and calpain activation were attenuated in rho- cells. Our data indicate that the apoptosis-inducing effect of C2-ceramide may require mitochondrial respiratory chain activity and can occur independently of the mitochondrial apoptosis pathway, but involves the activation of calpains. |
Databáze: | OpenAIRE |
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