Effect of glucosphingolipid synthesis inhibitor (PPMP and PDMP) treatment on Tetrahymena pyriformis: data on the evolution of the signaling system.

1-Phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) are structural analogues of ceramide; inhibiting UDP-glucose : ceramide glucosyltransferase. After treatment with these synthetic ceramide analogues the expression of glucosphingolipid decreases, while ceramide and sphingomyelin levels increase in the cells of higher eukaryotes. In the unicellular Tetrahymena pyriformis, treatment with PDMP (10-20 microM) and PPMP (40-80 microM) influenced the synthesis of galactose, glucosamine and mannose-containing lipids. On the whole the amount of these lipids was reduced, but new galactose and glucosamine-containing lipids appeared (the exact structures of these lipids were not characterized). Incorporation of (32)P into phosphatidylethanolamine (PE) and phosphatidic acid (PA) was decreased significantly; however the amount of inositol phospholipids were increased. The incorporation of 3H-serine into phosphatidylserine was abolished, but incorporation into sphingomyelin and ceramide was increased. The cytoskeletal elements (silver line system) were disturbed on the basis of scanning electron microscopic pictures. The TRITC-Con A binding and the morphology of the cells were influenced as revealed by confocal laser scanning microscopic analyses. In contrast to higher eukaryotes, in Tetrahymena the shorter fatty acyl chain variant (PDMP) proved to be more effective in each of the examined parameters, while the longer chain variants (PPMP) had milder activity. Copyright 2000 John Wiley & Sons, Ltd.