Sphingolipids as Signaling and Regulatory Molecules

Animal Models for Studying the Pathophysiology of Ceramide (Sphingolipids)

Abstract Bioactive sphingolipids play key roles in the regulation of several fundamental biological processes such as proliferation, apoptosis and transformation. The recent development of genetically engineered mouse (GEM) models has enabled the study of functional roles of sphingolipids in normal development and disease. In this topic, we review the phenotypes of GEM models (knockout mice) […]

Ceramide-1-Phosphate in Cell Survival and Inflammatory Signaling (Sphingolipids)

Abstract An important metabolite of ceramide is ceramide-1-phosphate (C1P). This lipid second messenger was first demonstrated to be mitogenic for fibroblasts and macrophages and later shown to have antiapoptotic properties. C1P is also an important mediator of the inflammatory response, by stimulating the release of arachidonic acid through activation of group IVA cytosolic phospholipase A2, […]

Ceramide-1-Phosphate in Phagocytosis and Calcium Homeostasis (Sphingolipids)

Abstract Sphingolipids are well established sources of important signaling molecules. For example, ceramide (Cer) has been described as a potent inhibitor of cell growth and inducer of apoptosis. In contrast, ceramide-1-phosphate (C1P) has been reported to have mitogenic properties and to inhibit apoptosis. Our understanding of the distinct biological roles of C1P in the regulation […]

Extracellular and Intracellular Actions of Sphingosine-1-Phosphate (Sphingolipids)

Abstract Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator with crucial roles in a wide variety of cellular functions across a broad range of organisms. Though a simple molecule in structure, S1P functions are complex. The formation of S1P is catalyzed by one of two sphingosine kinases that have differential cellular distributions as well as both […]

Glucosylceramide in Humans (Sphingolipids)

Abstract Glucosylceramide has a unique and often ambiguous role in mammalian cells. Activation of glucosylceramide synthase, the enzyme that places a glucosyl moiety onto ceramide, is the first pathway-committed step to the production of more complex glycosphingolipids such as lactosylceramide and gangliosides. Alterations in the level of glucosylceramide are noted in cells and tissues in […]

Gangliosides as Regulators of Cell Membrane Organization and Functions (Sphingolipids)

Abstract Gangliosides, characteristic complex lipids present in the external layer of plasma membranes, deeply influence the organization of the membrane as a whole and the function of specific membrane associated proteins due to lipid-lipid and lipid-protein lateral interaction. Here we discuss the basis for the membrane-organizing potential of gangliosides, examples of ganglioside-regulated membrane protein complexes […]

Cancer Treatment Strategies Targeting Sphingolipid Metabolism Part 1

Abstract Ceramide and sphingosine-1-phosphate are related sphingolipid metabolites that can be generated through a de novo biosynthetic route or derived from the recycling ofmembrane sphingomyelin. Both these lipids regulate cellular responses to stress, with generally opposing effects. Sphingosine-1-phosphate functions as a growth and survival factor, acting as a ligand for a family of G protein-coupled […]

Cancer Treatment Strategies Targeting Sphingolipid Metabolism Part 2

Sphingolipids and Autophagy In addition to regulating apoptosis and protein translation, the PI3K/AKT signaling pathway plays a central role in regulating autophagy, another important mechanism of cell death upon which sphingolipids exert their influence. Autophagy is the evolutionarily conserved lysosomal degradation of a cell’s own macromolecules and organelles. Autophagy is important in energy homeostasis, providing […]

Therapeutic Strategies for Diabetes and Complications: A Role for Sphingolipids?

Abstract Diabetes is a debilitating chronic disease that has no cure and can only be managed by pharmaceutical or nutritional interventions. Worldwide, the incidence of diabetes and diabetic complications is dramatically increasing. This may reflect the incomplete knowledge base underlying the role of inflammatory or nutritional stresses to exacerbate diabetic complications. Despite the knowledge that […]

Roles for Sphingolipids in Saccharomyces cerevisiae

Abstract Studies using Saccharomyces cerevisiae, the common baker’s or brewer’s yeast, have progressed over the past twenty years from knowing which sphingolipids are present in cells and a basic outline of how they are made to a complete or nearly complete directory of the genes that catalyze their anabolism and catabolism. In addition, cellular processes […]

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