TY  - JOUR
A1  - Vutukuri, Rajkumar
A1  - Koch, Alexander
A1  - Trautmann, Sandra
A1  - Schreiber, Yannick
A1  - Thomas, Dominique Jeanette
A1  - Mayser, Franziska
A1  - Meyer zu Heringdorf, Dagmar
A1  - Pfeilschifter, Josef
A1  - Pfeilschifter, Waltraud
A1  - Brunkhorst, Robert
T1  - S1P d20:1, an endogenous modulator of S1P d18:1/S1P2-dependent signaling
T2  - The FASEB journal
N2  - Sphingosine 1-phosphate (S1P) signaling influences numerous cell biological mechanisms such as differentiation, proliferation, survival, migration, and angiogenesis. Intriguingly, our current knowledge is based solely on the role of S1P with an 18-carbon long-chain base length, S1P d18:1. Depending on the composition of the first and rate-limiting enzyme of the sphingolipid de novo metabolism, the serine palmitoyltransferase, other chain lengths have been described in vivo. While cells are also able to produce S1P d20:1, its abundance and function remains elusive so far. Our experiments are highlighting the role of S1P d20:1 in the mouse central nervous system (CNS) and human glioblastoma. We show here that S1P d20:1 and its precursors are detectable in both healthy mouse CNS-tissue and human glioblastoma. On the functional level, we focused our work on one particular, well-characterized pathway, the induction of cyclooxygenase (COX)-2 expression via the S1P receptor 2 (S1P2). Intriguingly, S1P d20:1 only fairly induces COX-2 expression and can block the S1P d18:1-induced COX-2 expression mediated via S1P2 activation in the human glioblastoma cell line LN229. This data indicates that S1P d20:1 might act as an endogenous modulator of S1P signaling via a partial agonism at the S1P2 receptor. While our findings might stimulate further research on the relevance of long-chain base lengths in sphingolipid signaling, the metabolism of S1P d20:1 has to be considered as an integral part of S1P signaling pathways in vivo.
KW  - brain
KW  - cyclooxygenase 2
KW  - glioblastoma cells
KW  - S1P receptors
KW  - sphingosine 1-phosphate
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63827
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-638271
SN  - 1530-6860
N1  - This work was supported by the German Research Foundation (SFB 1039 to RB, WP, JP, DMzH), and the Foundation Leducq (to WP and JP).
VL  - 34
IS  - 3
SP  - 3932
EP  - 3942
PB  - Wiley
CY  - Hoboken, NJ
ER  -