Chasing sphingosine-1-phosphate, a lipid mediator for cardiomyocyte survival

Abstract

See article by Tao et al. [5] (pages 56–63) in this issue. Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite that regulates many essential biological processes in various cells and tissues. S1P may act as an extracellular ligand to specific G protein-coupled S1P receptors (S1P1–5) or as an intracellular second messenger. Sphingosine is derived from cleavage of ceramide by ceramidases in the sphingolipid degradative pathway. It can be catalyzed by sphingosine kinases (SphK1 and 2) into S1P, which is then degraded by a S1P lyase and S1P phosphohydrolases. S1P is most abundant in platelets, but it can also be synthesized in various cells such as cardiomyocytes. A “sphingolipid rheostat” hypothesis suggests that the relative levels of these lipids are important determinants of cell fate [1]. In fact, both ceramide and S1P are known to be involved in cardiomyocyte survival and apoptosis. It has been shown that ceramide induces cardiomyocyte apoptosis in the heart [2], and it has been proposed that it is a mediator of cardiomyocyte death in myocardial ischemic–reperfusion injury [3]. On the contrary, S1P exerts an anti-apoptosis effect in rat cultured neonatal cardiomyocytes [4]. … *Tel.: +1 404 756 5056; fax: +1 404 742 1042. Email address: qyang{at}msm.edu