An update on sphingosine-1-phosphate and other sphingolipid mediators.
Sphingolipids comprise a complex family of naturally occurring molecules that are enriched in lipid rafts and contribute to their unique biochemical properties. Membrane sphingolipids also serve as a reservoir for bioactive metabolites including sphingosine, ceramide, sphingosine-1-phosphate and ceramide-1-phosphate. Among these, sphingosine-1-phosphate has emerged as a central regulator of mammalian biology. Sphingosine-1-phosphate is essential for mammalian brain and cardiac development and for maturation of the systemic circulatory system and lymphatics. In addition, sphingosine-1-phosphate contributes to trafficking and effector functions of lymphocytes and other hematopoietic cells and protects against various forms of tissue injury. However, sphingosine-1-phosphate is also an oncogenic lipid that promotes tumor growth and progression. Recent preclinical and clinical investigations using pharmacological agents that target sphingosine-1-phosphate, its receptors and the enzymes required for its biosynthesis and degradation demonstrate the promise and potential risks of modulating sphingosine-1-phosphate signaling in treatment strategies for autoimmunity, cancer, cardiovascular disease and other pathological conditions.
Fyrst
Henrik
H
Center for Cancer Research, Children's Hospital Oakland Research Institute, Oakland, California, USA.
Saba
Julie D
JD
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008246:Lysophospholipids / Q000235:genetics / Q000378:metabolism*; D013107:Sphingolipids / Q000235:genetics / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism
D008246:Lysophospholipids; D013107:Sphingolipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine