ceramide as a second messenger is a key regulator in apoptosis and cytotoxicity. ceramide-metabolizing enzymes are ideal target in cancer chemo-preventive studies. neutral sphingomyelinase (nsmase), acid ceramidase (acdase) and glucosyl ceramide synthase (gcs) are the main enzymes in ceramide metabolism. silymarin flavonolignans are potent apoptosis inducers and silibinin is the most active com...

Despite of the importance of the acid sphingomyelinase for sphingomyelin homeostasis and sphingolipid signalling, potent and selective inhibitors for this enzyme are rare. An increasing set of data on the inhibition of acid sphingomyelinase in different disease models using indirect inhibitors has been generated and strongly implies acid sphingomyelinase as an emerging drug target. Very recentl...

Pathogenic members of the genus Leptospira are the causative agents of leptospirosis, a neglected disease of public and veterinary health concern. Leptospirosis is a systemic disease that in its severest forms leads to renal insufficiency, hepatic dysfunction, and pulmonary failure. Many strains of Leptospira produce hemolytic and sphingomyelinase activities, and a number of candidate leptospir...

The effects of sphingomyelinase, phosphorylcholine, N-acetylsphingosine (C2-ceramide), N-hexanoylsphingosine (C6-ceramide) and sphingosine on basal and insulin-stimulated cellular accumulation of 2-deoxy-D-glucose in rat soleus muscles were investigated. Preincubation of muscles with sphingomyelinase (100 or 200 m-units/ml) for 1 or 2 h augmented basal 2-deoxyglucose uptake by 29-91%, and that ...

A basis for the insulin mimetic effect of sphingomyelinase on glucose transporter isoform GLUT4 translocation remains unclear. Because sphingomyelin serves as a major determinant of plasma membrane cholesterol and a relationship between plasma membrane cholesterol and GLUT4 levels has recently become apparent, we assessed whether GLUT4 translocation induced by sphingomyelinase resulted from cha...

The cell membrane contains very small distinct membrane domains enriched of sphingomyelin and cholesterol that are named rafts. We have shown that the formation of ceramide via activation of the acid sphingomyelinase transforms rafts into ceramide-enriched membrane platforms. These platforms are required for infection of mammalian cells with Pseudomonas aeruginosa, Staphylococcus aureus, or Nei...

Plasmodia express a sphingomyelinase, which is apparently required for their development. On the other hand, the sphingomyelinase product ceramide has previously been shown to delay parasite development. Moreover, ceramide triggers suicidal erythrocyte death or eryptosis, characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. Accelerated eryptosis of infe...

Eryptosis, the suicidal erythrocyte death, leads to cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Eryptotic erythrocytes adhere to the vascular wall by binding of phosphatidylserine to the CXC chemokine ligand 16 (CXCL16). Stimulators of eryptosis include increased cytosolic Ca(2+) activity, energy depletion, and activation of ceramide-produci...

The interaction with human phagocytes is a hallmark of symptomatic Neisseria gonorrhoeae infections. Gonococcal outer membrane proteins of the Opa family induce the opsonin-independent uptake of the bacteria that relies on CEACAM receptors and an active signaling machinery of the phagocyte. Here, we show that CEACAM receptor-mediated phagocytosis of Opa(52)-expressing N. gonorrhoeae into human ...

Apolipoprotein (apo)C-III-1 from human very low density lipoprotein stimulates 14-fold the activity of lysosomal sphingomyelinase from human fibroblasts. At the sphingomyelin concentrations tested, maximal stimulation was obtained with 5 microM apoC-III-1 or apoC mixture. Apolipoproteins A-I, A-II, B, and C-I conferred little or no stimulation. Sphingomyelinase was stimulated 20-fold by lysopho...