TY  - GEN
A1  - Polzin, Amin
A1  - Rassaf, Tienush
A1  - Boehm, Andreas
A1  - Lueth, Anja
A1  - Kleuser, Burkhard
A1  - Zeus, Tobias
A1  - Kelm, Malte
A1  - Kroemer, Heyo K.
A1  - Schroer, Karsten
A1  - Rauch, Bernhard H.
T1  - Aspirin inhibits release of platelet-derived sphingosine-1-phosphate in
 acute myocardial infarction
T2  - INTERNATIONAL JOURNAL OF CARDIOLOGY
KW  - Sphingosine-1-phosphate
KW  - Acute coronary syndrome
KW  - Platelets
KW  - Aspirin
Y1  - 2013
U6  - https://doi.org/10.1016/j.ijcard.2013.10.050
SN  - 0167-5273
SN  - 1874-1754
VL  - 170
IS  - 2
SP  - E23
EP  - E24
PB  - ELSEVIER IRELAND LTD
CY  - CLARE
ER  - 
TY  - JOUR
A1  - Gulbins, Erich
A1  - Palmada, Monica
A1  - Reichel, Martin
A1  - Lueth, Anja
A1  - Boehmer, Christoph
A1  - Amato, Davide
A1  - Mueller, Christian P.
A1  - Tischbirek, Carsten H.
A1  - Groemer, Teja W.
A1  - Tabatabai, Ghazaleh
A1  - Becker, Katrin Anne
A1  - Tripal, Philipp
A1  - Staedtler, Sven
A1  - Ackermann, Teresa F.
A1  - van Brederode, Johannes
A1  - Alzheimer, Christian
A1  - Weller, Michael
A1  - Lang, Undine E.
A1  - Kleuser, Burkhard
A1  - Grassme, Heike
A1  - Kornhuber, Johannes
T1  - Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs
JF  - Nature medicine
N2  - Major depression is a highly prevalent severe mood disorder that is treated with antidepressants. The molecular targets of antidepressants require definition. We investigated the role of the acid sphingomyelinase (Asm)-ceramide system as a target for antidepressants. Therapeutic concentrations of the antidepressants amitriptyline and fluoxetine reduced Asm activity and ceramide concentrations in the hippocampus, increased neuronal proliferation, maturation and survival and improved behavior in mouse models of stress-induced depression. Genetic Asm deficiency abrogated these effects. Mice overexpressing Asm, heterozygous for acid ceramidase, treated with blockers of ceramide metabolism or directly injected with C16 ceramide in the hippocampus had higher ceramide concentrations and lower rates of neuronal proliferation, maturation and survival compared with controls and showed depression-like behavior even in the absence of stress. The decrease of ceramide abundance achieved by antidepressant-mediated inhibition of Asm normalized these effects. Lowering ceramide abundance may thus be a central goal for the future development of antidepressants.
Y1  - 2013
U6  - https://doi.org/10.1038/nm.3214
SN  - 1078-8956
VL  - 19
IS  - 7
SP  - 934
EP  - +
PB  - Nature Publ. Group
CY  - New York
ER  - 
TY  - CHAP
A1  - Boehm, Andreas
A1  - Polzin, A.
A1  - Lueth, Anja
A1  - Kleuser, Burkhard
A1  - Rassaf, T.
A1  - Kelm, M.
A1  - Kroemer, H. K.
A1  - Schroer, K.
A1  - Rauch, B. H.
T1  - The release of sphingosine-1-phosphate from human platelets during acute coronary syndrome is attenuated by aspirin
T2  - NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
Y1  - 2012
SN  - 0028-1298
VL  - 385
SP  - 12
EP  - 12
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Keller, Johannes
A1  - Catala-Lehnen, Philip
A1  - Huebner, Antje K.
A1  - Jeschke, Anke
A1  - Heckt, Timo
A1  - Lueth, Anja
A1  - Krause, Matthias
A1  - Koehne, Till
A1  - Albers, Joachim
A1  - Schulze, Jochen
A1  - Schilling, Sarah
A1  - Haberland, Michael
A1  - Denninger, Hannah
A1  - Neven, Mona
A1  - Hermans-Borgmeyer, Irm
A1  - Streichert, Thomas
A1  - Breer, Stefan
A1  - Barvencik, Florian
A1  - Levkau, Bodo
A1  - Rathkolb, Birgit
A1  - Wolf, Eckhard
A1  - Calzada-Wack, Julia
A1  - Neff, Frauke
A1  - Gailus-Durner, Valerie
A1  - Fuchs, Helmut
A1  - de Angelis, Martin Hrabe
A1  - Klutmann, Susanne
A1  - Tsourdi, Elena
A1  - Hofbauer, Lorenz C.
A1  - Kleuser, Burkhard
A1  - Chun, Jerold
A1  - Schinke, Thorsten
A1  - Amling, Michael
T1  - Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts
JF  - Nature Communications
N2  - The hormone calcitonin (CT) is primarily known for its pharmacologic action as an inhibitor of bone resorption, yet CT-deficient mice display increased bone formation. These findings raised the question about the underlying cellular and molecular mechanism of CT action. Here we show that either ubiquitous or osteoclast-specific inactivation of the murine CT receptor (CTR) causes increased bone formation. CT negatively regulates the osteoclast expression of Spns2 gene, which encodes a transporter for the signalling lipid sphingosine 1-phosphate (S1P). CTR-deficient mice show increased S1P levels, and their skeletal phenotype is normalized by deletion of the S1P receptor S1P(3). Finally, pharmacologic treatment with the nonselective S1P receptor agonist FTY720 causes increased bone formation in wild-type, but not in S1P(3)-deficient mice. This study redefines the role of CT in skeletal biology, confirms that S1P acts as an osteoanabolic molecule in vivo and provides evidence for a pharmacologically exploitable crosstalk between osteoclasts and osteoblasts.
Y1  - 2014
U6  - https://doi.org/10.1038/ncomms6215
SN  - 2041-1723
VL  - 5
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Barcelo-Coblijn, Gwendolyn
A1  - Laura Martin, Maria
A1  - de Almeida, Rodrigo F. M.
A1  - Antonia Noguera-Salva, Maria
A1  - Marcilla-Etxenike, Amaia
A1  - Guardiola-Serrano, Francisca
A1  - Lueth, Anja
A1  - Kleuser, Burkhard
A1  - Halver, John E.
A1  - Escriba, Pablo V.
T1  - Sphingomyelin and sphingomyelin synthase (SMS) in the malignant transformation of glioma cells and in 2-hydroxyoleic acid therapy
JF  - Proceedings of the National Academy of Sciences of the United States of America
N2  - The mechanism of action of 2-hydroxyoleic acid (2OHOA), a potent antitumor compound, has not yet been fully elucidated. Here, we show that human cancer cells have markedly lower levels of sphingomyelin (SM) than nontumor (MRC-5) cells. In this context, 2OHOA treatment strongly augments SM mass (4.6-fold), restoring the levels found in MRC-5 cells, while a loss of phosphatidylethanolamine and phosphatidylcholine is observed (57 and 30%, respectively). The increased SM mass was due to a rapid and highly specific activation of SM synthases (SMS). This effect appeared to be specific against cancer cells as it did not affect nontumor MRC-5 cells. Therefore, low SM levels are associated with the tumorigenic transformation that produces cancer cells. SM accumulation occurred at the plasma membrane and caused an increase in membrane global order and lipid raft packing in model membranes. These modifications would account for the observed alteration by 2OHOA in the localization of proteins involved in cell apoptosis (Fas receptor) or differentiation (Ras). Importantly, SMS inhibition by D609 diminished 2OHOA effect on cell cycle. Therefore, we propose that the regulation of SMS activity in tumor cells is a critical upstream event in 2OHOA antitumor mechanism, which also explains its specificity for cancer cells, its potency, and the lack of undesired side effects. Finally, the specific activation of SMS explains the ability of this compound to trigger cell cycle arrest, cell differentiation, and autophagy or apoptosis in cancer cells.
KW  - anticancer
KW  - membrane-lipid therapy
KW  - lung cancer
KW  - membrane lipids
Y1  - 2011
U6  - https://doi.org/10.1073/pnas.1115484108
SN  - 0027-8424
VL  - 108
IS  - 49
SP  - 19569
EP  - 19574
PB  - National Acad. of Sciences
CY  - Washington
ER  -