Serine Palmitoyltransferase Regulates de NovoCeramide Generation during Etoposide-induced Apoptosis
| Autor: | Jill M. Carton, David K. Perry, David J. Uhlinger, Yusuf A. Hannun, Amit K. Shah, Filmore I. Meredith |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Ceramide
Proteolysis Palmitates Serine C-Palmitoyltransferase Apoptosis Biology Ceramides Models Biological Biochemistry chemistry.chemical_compound Sphingosine Microsomes Tumor Cells Cultured medicine Humans Protease Inhibitors Molecular Biology Etoposide Leukemia medicine.diagnostic_test Serine C-palmitoyltransferase Biological Transport Trypan Blue Cell Biology Lipid signaling Mycotoxins Antineoplastic Agents Phytogenic Cell biology Enzyme Activation De novo synthesis chemistry Caspases Poly(ADP-ribose) Polymerases Oxidoreductases Sphingomyelin Acyltransferases medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 275:9078-9084 |
| ISSN: | 0021-9258 |
| Popis: | The de novo pathway of sphingolipid synthesis has been identified recently as a novel means of generating ceramide during apoptosis. Furthermore, it has been suggested that the activation of dihydroceramide synthase is responsible for increased ceramide production through this pathway. In this study, accumulation of ceramide mass in Molt-4 human leukemia cells by the chemotherapy agent etoposide was found to occur primarily due to activation of the de novo pathway. However, when the cells were labeled with a substrate for dihydroceramide synthase in the presence of etoposide, there was no corresponding increase in labeled ceramide. Further investigation using a labeled substrate for serine palmitoyltransferase, the rate-limiting enzyme in the pathway, resulted in an accumulation of label in ceramide upon etoposide treatment. This result suggests that the activation of serine palmitoyltransferase is the event responsible for increased ceramide generation during de novo synthesis initiated by etoposide. Importantly, the ceramide generated from de novo synthesis appears to have a distinct function from that induced by sphingomyelinase action in that it is not involved in caspase-induced poly (ADP-ribose)polymerase proteolysis but does play a role in disrupting membrane integrity in this model system. These results implicate serine palmitoyltransferase as the enzyme controlling de novo ceramide synthesis during apoptosis and begin to define a unique function of ceramide generated from this pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|