fumonisin-b1 and Niemann-Pick-Diseases

Stress-induced activation of an acidic sphingomyelinase leading to generation of ceramide, an important lipid mediator, has been associated with apoptosis; however, the implication of this hydrolase has been questioned. The present study aimed at re-evaluating the role of this lysosomal enzyme in apoptosis initiated by different apoptotic inducers. The sensitivity of a series of acid sphingomyelinase-deficient cell lines derived from Niemann-Pick disease patients to stress-induced apoptosis was investigated. We have now shown that stress stimuli, such as anthracyclines, ionizing radiation, and Fas ligation trigger similar apoptotic hallmarks in normal and acid sphingomyelinase-deficient cell lines. Retrovirus-mediated gene correction of enzyme deficiency in Niemann-Pick cells does not modify response to apoptosis. Ceramide production is comparable in normal and Niemann-Pick cells, and increased activity of neutral sphingomyelinase is observed. Thus, our findings cast serious doubts that lysosomal sphingomyelinase activation is responsible for stress-induced apoptosis of cultured cells.

Topics: Apoptosis; Carboxylic Acids; Caspase 3; Caspases; Cell Line; Cell Survival; Ceramides; Daunorubicin; Doxorubicin; Enzyme Inhibitors; fas Receptor; Fumonisins; Humans; Lymphocytes; Lysosomes; Niemann-Pick Diseases; Peptide Hydrolases; Reference Values; Sphingomyelin Phosphodiesterase