Involvement of the acid sphingomyelinase pathway in UVA-induced apoptosis

The sphingomyelin-ceramide pathway is an evolutionarily conserved ubiquitou s signal transduction system that regulates many cell functions including a poptosis. Sphingomyelin (SM) is hydrolyzed to ceramide by different sphingo myelinases. Ceramide serves as a second messenger in mediating cellular eff ects of cytokines and stress. In this study, we find that acid sphingomyeli nase (SMase) activity was induced by UVA in normal JY lymphoblasts but was not detectable in MS1418 lymphoblasts from Niemann-Pick type D patients who have an inherited deficiency of acid SMase. We also provide evidence that WA can induce apoptosis by activating acid SMase in normal JY cells. In con trast, UVA-induced apoptosis was inhibited in MS1418 cells. Exogenous SMase and its product, ceramide (10-40 muM), induced apoptosis in JY and MS1418 cells, but the substrate of SMase, SM (20-80 muM), induced apoptosis only i n JY cells. These results suggest that UVA-induced apoptosis by SM is depen dent on acid SMase activity. We also provide evidence that induction of apo ptosis by WA may occur through activation of JNKs via the acid SMase pathwa y.