Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate.

Ceramide is an important lipid signaling molecule and a key intermediate in sphingolipid biosynthesis. Recent studies have implied a previously unappreciated role for the ceramide N-acyl chain length, inasmuch as ceramides containing specific fatty acids appear to play defined roles in cell physiology. The discovery of a family of mammalian ceramide synthases (CerS), each of which utilizes a restricted subset of acyl-CoAs for ceramide synthesis, strengthens this notion.

Potential new antimalarial chemotherapeutics based on sphingolipid metabolism.

The discovery of new antimalarial drugs is mandatory to improve the effectiveness of antimalarial prophylaxis and treatment. In this review, we focused on sphingolipids as potential new targets for antimalarial drugs. Inhibition of sphingomyelin and/or glucosylceramide synthases leads to increased intracellular concentrations of ceramide and results in growth inhibition of Plasmodium falciparum.

Glycosphingolipidoses: beyond the enzymatic defect.

The glycosphingolipid lysosomal storage diseases are a group of monogenic human disorders caused by the impaired catalytic activity of enzymes responsible for glycosphingolipid catabolism. Clinical presentation of the diseases is heterogeneous, with little obvious correlation between the kind of accumulating glycosphingolipid and disease progression or pathogenesis. In this review, we discuss clinical symptoms of this group of diseases, and attempt to link disease progression and pathology with the biochemical and cellular pathways that may be potentially altered in the diseases.

The antiparasitic actions of plant jasmonates.

Jasmonates are a group of small lipids produced in plants, which function as plant stress hormones. We have previously shown that jasmonates can exert significant cytotoxic effects upon human cancer cells. The purpose of the present study was to determine the effects of jasmonates on parasites.

Ceramide mediates growth inhibition of the Plasmodium falciparum parasite.

In mammalian cells, ceramide mediates death by chemotherapeutic drugs. We analysed, for the first time, the role of ceramide in inhibiting growth of the malaria-causing parasite Plasmodium falciparum. Added exogenously, ceramide significantly decreased the number of parasites, and this effect was abolished by sphingosine-1-phosphate, a biological antagonist of ceramide action.

Selective susceptibility of transformed T lymphocytes to induction of apoptosis by PSC 833, an inhibitor of P-glycoprotein.

P-glycoprotein is a cellular efflux pump. The P-glycoprotein inhibitor PSC 833 causes apoptosis of cancer cells and induces a rise in the intracellular levels of ceramide. Our aims were to determine whether a cause and effect relationship exists between these two actions of PSC 833, and to assess whether the PSC 833-induced apoptosis is restricted to transformed cells.