S1P d20:1, an endogenous modulator of S1P d18:1/S1P2-dependent signaling

  • 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.

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Author:Rajkumar Vutukuri, Alexander Koch, Sandra Trautmann, Yannick Schreiber, Dominique Jeanette ThomasORCiDGND, Franziska Mayser, Dagmar Meyer zu Heringdorf, Josef PfeilschifterGND, Waltraud PfeilschifterORCiDGND, Robert BrunkhorstGND
Parent Title (English):The FASEB journal
Place of publication:Hoboken, NJ
Document Type:Article
Date of Publication (online):2020/01/15
Date of first Publication:2020/01/15
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2022/03/08
Tag:S1P receptors; brain; cyclooxygenase 2; glioblastoma cells; sphingosine 1-phosphate
Page Number:11
First Page:3932
Last Page:3942
This work was supported by the German Research Foundation (SFB 1039 to RB, WP, JP, DMzH), and the Foundation Leducq (to WP and JP).
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0