The Coordination of Prostaglandin E 2 Production by Sphingosine-1-phosphate and Ceramide-1-phosphate

ABSTRACT The ability of pro-inflammatory cytokines such as interleukin-1␤ (IL-1␤) to induce the major inflammatory mediator prostaglandin (PG) E 2 depends on the activation of two rate-limiting enzymes, phospholipase A 2 (PLA 2 ) and cyclooxygenase 2 (COX-2). PLA 2 acts to generate arachidonic acid, which serves as the precursor substrate for COX-2 in the metabolic pathway leading to PGE 2 production. However, less is known about the mechanisms that coordinate the regulation of these two enzymes. We have provided prior evidence that sphingosine kinase 1 and its bioactive lipid product sphingosine-1-phosphate (S1P) mediate the effects of cytokines on COX-2 induction, whereas ceramide kinase and its distinct product, ceramide-1-phosphate (C1P), are required for the activation and translocation of cPLA 2 (FASE

Association of New Loci Identified in European Genome-Wide Association Studies with Susceptibility to Type 2 Diabetes in the Japanese

Several novel susceptibility loci for type 2 diabetes have been identified through genome-wide association studies (GWAS) for type 2 diabetes or quantitative traits related to glucose metabolism in European populations. To investigate the association of the 13 new European GWAS-derived susceptibility loci with type 2 diabetes in the Japanese population, we conducted a replication study using 3 independent Japanese case-control studies. locus, had nominal association with type 2 diabetes in the present Japanese samples (P<0.05). locus may be common locus for type 2 diabetes across different ethnicities

The Impact of Sphingosine Kinase-1 in Head and Neck Cancer

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