Evidence for the association of ultraviolet-C and H(2)O(2)-induced apoptosis with acid sphingomyelinase activation.
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).
Komatsu
M
M
Department of Pediatrics, Akita University School of Medicine, Japan.
Takahashi
T
T
Abe
T
T
Takahashi
I
I
Ida
H
H
Takada
G
G
D017398:Alternative Splicing; D017209:Apoptosis; D002461:Cell Line, Transformed; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008214:Lymphocytes / Q000378:metabolism; D009154:Mutation; D009542:Niemann-Pick Diseases / Q000201:enzymology / Q000235:genetics; D010375:Pedigree; D013108:Sphingomyelin Phosphodiesterase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
D006861:Hydrogen Peroxide; C112980:acid sphingomyelinase-1; D013108:Sphingomyelin Phosphodiesterase