The role of ceramide in receptor- and stress-induced apoptosis studied in acidic ceramidase-deficient Farber disease cells

The activation of sphingomyelinases leading to the generation of ceramide h as been implicated in various apoptotic pathways. However, the role of cera mide as an essential death mediator remains highly controversial. In the pr esent study, we investigated the functional relevance of ceramide in a gene tic model by using primary cells from a Farber disease patient. These cells accumulate ceramide as the result of an inherited deficiency of acidic cer amidase. We demonstrate that Farber disease lymphocytes and fibroblasts und erwent apoptosis induced by various stress stimuli, including staurosporine , anticancer drugs and gamma -irradiation, equally as normal control cells. In addition, caspase activation by these proapoptotic agents occurred rath er similarly in Farber disease and control fibroblasts. Interestingly, Farb er disease lymphoid cells underwent apoptosis induced by the CD95 death rec eptor more rapidly than control cells. Our data therefore suggest that cera mide does not play an essential role as a second messenger in stress-induce d apoptosis. However, in accordance with a role in lipid-rich microdomains, ceramide by altering membrane composition may function as an amplifier in CD95-mediated apoptosis.