The activation of sphingomyelinases leading to the generation of
ceramide has been implicated in various apoptotic pathways. However, the role of
ceramide as an essential death mediator remains highly controversial. In the present study, we investigated the functional relevance of
ceramide in a genetic model by using primary cells from a
Farber disease patient. These cells accumulate
ceramide as the result of an inherited deficiency of acidic
ceramidase. We demonstrate that
Farber disease lymphocytes and fibroblasts underwent 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 rather similarly in
Farber disease and control fibroblasts. Interestingly,
Farber disease lymphoid cells underwent apoptosis induced by the CD95
death receptor more rapidly than control cells. Our data therefore suggest that
ceramide does not play an essential role as a second messenger in stress-induced 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.