@article{EderHollmannMandasarietal.2022, author = {Eder, Sascha and Hollmann, Claudia and Mandasari, Putri and Wittmann, Pia and Schumacher, Fabian and Kleuser, Burkhard and Fink, Julian and Seibel, J{\"u}rgen and Schneider-Schaulies, J{\"u}rgen and Stigloher, Christian and Beyersdorf, Niklas and Dembski, Sofia}, title = {Synthesis and characterization of ceramide-containing liposomes as membrane models for different T cell subpopulations}, series = {Journal of Functional Biomaterials}, volume = {13}, journal = {Journal of Functional Biomaterials}, number = {3}, issn = {2079-4983}, doi = {10.3390/jfb13030111}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286130}, year = {2022}, abstract = {A fine balance of regulatory (T\(_{reg}\)) and conventional CD4\(^+\) T cells (T\(_{conv}\)) is required to prevent harmful immune responses, while at the same time ensuring the development of protective immunity against pathogens. As for many cellular processes, sphingolipid metabolism also crucially modulates the T\(_{reg}\)/T\(_{conv}\) balance. However, our understanding of how sphingolipid metabolism is involved in T cell biology is still evolving and a better characterization of the tools at hand is required to advance the field. Therefore, we established a reductionist liposomal membrane model system to imitate the plasma membrane of mouse T\(_{reg}\) and T\(_{conv}\) with regards to their ceramide content. We found that the capacity of membranes to incorporate externally added azide-functionalized ceramide positively correlated with the ceramide content of the liposomes. Moreover, we studied the impact of the different liposomal preparations on primary mouse splenocytes in vitro. The addition of liposomes to resting, but not activated, splenocytes maintained viability with liposomes containing high amounts of C\(_{16}\)-ceramide being most efficient. Our data thus suggest that differences in ceramide post-incorporation into T\(_{reg}\) and T\(_{conv}\) reflect differences in the ceramide content of cellular membranes.}, language = {en} } @article{AbdelhameedHabibEltahawyetal.2020, author = {Abdelhameed, Reda F. A. and Habib, Eman S. and Eltahawy, Nermeen A. and Hassanean, Hashim A. and Ibrahim, Amany K. and Mohammed, Anber F. and Fayez, Shaimaa and Hayallah, Alaa M. and Yamada, Koji and Behery, Fathy A. and Al-Sanea, Mohammad M. and Alzarea, Sami I. and Bringmann, Gerhard and Ahmed, Safwat A. and Abdelmohsen, Usama Ramadan}, title = {New cytotoxic natural products from the Red Sea sponge Stylissa carteri}, series = {Marine Drugs}, volume = {18}, journal = {Marine Drugs}, number = {5}, issn = {1660-3397}, doi = {10.3390/md18050241}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205795}, year = {2020}, abstract = {Bioactivity-guided isolation supported by LC-HRESIMS metabolic profiling led to the isolation of two new compounds, a ceramide, stylissamide A (1), and a cerebroside, stylissoside A (2), from the methanol extract of the Red Sea sponge Stylissa carteri. Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The bioactive extract's metabolomic profiling showed the existence of various secondary metabolites, mainly oleanane-type saponins, phenolic diterpenes, and lupane triterpenes. The in vitro cytotoxic activity of the isolated compounds was tested against two human cancer cell lines, MCF-7 and HepG2. Both compounds, 1 and 2, displayed strong cytotoxicity against the MCF-7 cell line, with IC\(_{50}\) values at 21.1 ± 0.17 µM and 27.5 ± 0.18 µM, respectively. They likewise showed a promising activity against HepG2 with IC\(_{50}\) at 36.8 ± 0.16 µM for 1 and IC\(_{50}\) 30.5 ± 0.23 µM for 2 compared to the standard drug cisplatin. Molecular docking experiments showed that 1 and 2 displayed high affinity to the SET protein and to inhibitor 2 of protein phosphatase 2A (I2PP2A), which could be a possible mechanism for their cytotoxic activity. This paper spreads light on the role of these metabolites in holding fouling organisms away from the outer surface of the sponge, and the potential use of these defensive molecules in the production of novel anticancer agents.}, language = {en} } @article{BecamWalterBurgertetal.2017, author = {Becam, J{\´e}r{\^o}me and Walter, Tim and Burgert, Anne and Schlegel, Jan and Sauer, Markus and Seibel, J{\"u}rgen and Schubert-Unkmeir, Alexandra}, title = {Antibacterial activity of ceramide and ceramide analogs against pathogenic Neisseria}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/s41598-017-18071-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159367}, pages = {17627}, year = {2017}, abstract = {Certain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C\(_{6}\) and long-chain C\(_{16}\)-ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) demonstrated that short-chain ceramides and a ω-azido-functionalized C\(_{6}\)-ceramide were active against Neisseria meningitidis and N. gonorrhoeae, whereas they were inactive against Escherichia coli and Staphylococcus aureus. Kinetic assays showed that killing of N. meningitidis occurred within 2 h with ω-azido-C\(_{6}\)-ceramide at 1 X the MIC. Of note, at a bactericidal concentration, ω-azido-C\(_{6}\)-ceramide had no significant toxic effect on host cells. Moreover, lipid uptake and localization was studied by flow cytometry and confocal laser scanning microscopy (CLSM) and revealed a rapid uptake by bacteria within 5 min. CLSM and super-resolution fluorescence imaging by direct stochastic optical reconstruction microscopy demonstrated homogeneous distribution of ceramide analogs in the bacterial membrane. Taken together, these data demonstrate the potent bactericidal activity of sphingosine and synthetic short-chain ceramide analogs against pathogenic Neisseriae.}, language = {en} }