Ceramide appears to be a potent second messenger implicated in the regulation of diverse cellular processes such as cell growth and differentiation, gene transcription,
ligand binding, and cell death. Environmental stress-induced apoptosis is believed to be associated with the
sphingomyelin degradation pathway, which generates
ceramide as a second messenger in initiating the apoptosis response. To date, two distinct sphingomyelinases, a lysosomal
acid sphingomyelinase (ASM), which is deficient in patients affected with types A and B
Niemann-Pick disease (
NPD), and a neutral,
magnesium-dependent
sphingomyelinase (NSM), are candidate
enzymes which respond to apoptotic stimulations and cause
sphingomyelin hydrolysis and subsequent
ceramide generation. Using Epstein-Barr virus (EBV)-transformed lymphoblast cells from type A
NPD patient which have defined splicing site mutation in the ASM gene, we showed that ASM-deficient cells were defective in ultraviolet-C (UV-C) and
hydrogen peroxide (H(2)O(2)) induced apoptosis. As another induction of apoptosis, we exposed this cell line to serum
starvation which influences to p53 expression and leads to apoptosis. There were no differences by the degree of apoptosis between ASM-deficient lymphoblast cells and normal lymphoblast cells. These results are evidence that ASM plays one of the important roles in apoptosis induction by UV-C and H(2)O(2).