Laura Martin, Maria and Liebisch, Gerhard and Lehneis, Stefan and Schmitz, Gerd and Alonso-Sande, Maria and Bestard-Escalas, Joan and Lopez, Daniel H. and Manuel Garcia-Verdugo, Jose and Soriano-Navarro, Mario and Busquets, Xavier and Escriba, Pablo V. and Barcelo-Coblijn, Gwendolyn (2013) Sustained activation of sphingomyelin synthase by 2-hydroxyoleic acid induces sphingolipidosis in tumor cells. JOURNAL OF LIPID RESEARCH, 54 (5). pp. 1457-1465. ISSN 0022-2275,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TANDEM MASS-SPECTROMETRY; ANTICANCER ACTIVITY; CERAMIDE; APOPTOSIS; METABOLISM; MINERVAL; PATHWAY; LIPIDS; DIFFERENTIATION; INDUCTION; antitumor drug; sphingolipid metabolism; mass spectroscopy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Apr 2020 07:37 |
| Last Modified: | 16 Apr 2020 07:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16775 |
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