Sustained activation of sphingomyelin synthase by 2-hydroxyoleic acid induces sphingolipidosis in tumor cells
| العنوان: | Sustained activation of sphingomyelin synthase by 2-hydroxyoleic acid induces sphingolipidosis in tumor cells |
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| المؤلفون: | Joan Bestard-Escalas, Pablo V. Escribá, Mario Soriano-Navarro, Stefan Lehneis, Maria Laura Martin, Gerd Schmitz, Daniel H. Lopez, Xavier Busquets, José Manuel García-Verdugo, Gwendolyn Barceló-Coblijn, María Alonso-Sande, Gerhard Liebisch |
| المصدر: | JOURNAL OF LIPID RESEARCH r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) instname r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Centro de Investigación Principe Felipe (CIPF) The Journal of Lipid Research; Vol 54 |
| بيانات النشر: | American Society for Biochemistry and Molecular Biology Inc., 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | 0303 health sciences, 030302 biochemistry & molecular biology, Cell Biology, Metabolism, Biology, antitumor drug, Biochemistry, Sphingolipid, 03 medical and health sciences, Endocrinology, Mechanism of action, Cell culture, 2-Hydroxyoleic Acid, sphingolipid metabolism, Sphingomyelin synthase, medicine, biology.protein, mass spectroscopy, Sphingolipidosis, lipids (amino acids, peptides, and proteins), Viability assay, medicine.symptom, 030304 developmental biology |
| الوصف: | The mechanism of action of 2-hydroxyoleic acid (2OHOA), a potent antitumor drug, involves the rapid and specific activation of sphingomyelin synthase (SMS), leading to a 4-fold increase in SM mass in tumor cells. In the present study, we investigated the source of the ceramides required to sustain this dramatic increase in SM. Through radioactive and fluorescent labeling, we demonstrated that sphingolipid metabolism was altered by a 24 h exposure to 2OHOA, and we observed a consistent increase in the number of lysosomes and the presence of unidentified storage materials in treated cells. Mass spectroscopy revealed that different sphingolipid classes accumulated in human glioma U118 cells after exposure to 2OHOA, demonstrating a specific effect on C16-, C20-, and C22-containing sphingolipids. Based on these findings, we propose that the demand for ceramides required to sustain the SMS activation (ca. 200-fold higher than the basal level) profoundly modifies both sphingolipid and phospholipid metabolism. As the treatment is prolonged, tumor cells fail to adequately metabolize sphingolipids, leading to a situation resembling sphingolipidosis, whereby cell viability is compromised.-Martin, M. L., G. Liebisch, S. Lehneis, G. Schmitz, M. Alonso-Sande, J. Bestard-Escalas, D. H. Lopez, J. M. Garcia-Verdugo, M. Soriano-Navarro, X. Busquets, P. V. Escriba, and G. Barcelo-Coblijn. Sustained activation of sphingomyelin synthase by 2-hydroxyoleic acid induces sphingolipidosis in tumor cells. J. Lipid Res. 2013. 54: 1457-1465. |
| تدمد: | 0022-2275 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aa8b0ab32d291fc649c59d66affdc39b https://fundanet.cipf.es/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2028 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....aa8b0ab32d291fc649c59d66affdc39b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00222275 |
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