Evidence for the association of ultraviolet-C and H2O2-induced apoptosis with acid sphingomyelinase activation

Ceramide appears to be a potent second messenger implicated in the regulati on of diverse cellular processes such as cell growth and differentiation, g ene transcription, ligand binding, and cell death. Environmental stress-ind uced apoptosis is believed to be associated with the sphingomyelin degradat ion pathway, which generates ceramide as a second messenger in initiating t he 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-dependen t sphingomyelinase (NSM), are candidate enzymes which respond to apoptotic. stimulations and cause sphingomyelin hydrolysis and subsequent ceramide ge neration. Using Epstein-Barr virus (EBV)-transformed lymphoblast cells from type A NPD patient which have defined splicing site mutation in the ASM ge ne, we showed that ASM-deficient cells were defective in ultraviolet-C (UV- C) and hydrogen peroxide (H2O2) induced apoptosis. As another induction of apoptosis, we exposed this cell line to serum starvation which influences t o p53 expression and leads to apoptosis. There were no differences by the d egree of apoptosis between ASM-deficient lymphoblast cells and normal lymph oblast. cells. These results are evidence that ASM plays one of the importa nt roles in apoptosis induction by UV-C and H2O2. (C) 2001 Elsevier Science BY. All rights reserved.