SPHINGOLIPID ACTIVATOR PROTEIN-D (SAP-D) STIMULATES THE LYSOSOMAL DEGRADATION OF CERAMIDE IN-VIVO

Glycosphingolipids of cultured fibroblasts from patients with total sp hingolipid activator proteins (SAPs) deficiency (Schnabel et al. J. Bi ol. Chem. 267:3312-3315, 1992) were labeled biosynthetically with [C-1 4]serine. After a chase period of 120h the patients' fibroblasts showe d increased labeling of ceramide, glucosylceramide, lactosylceramide a nd ganglioside G(M3) in comparison to normal control cells. Addition o f sap-D to the chase-media of the patients' fibroblasts led to the deg radation of the accumulated ceramide down to nearly normal levels, whe reas the levels of other labeled sphingolipids remained unaffected. In contrast, addition of sap-B to the chase-media of the patients' fibro blasts did not reduce the increased ceramide levels but resulted, as e xpected from in vitro experiments, in a specific decrease of levels of lactosylceramide and ganglioside G(M3) Therefore,we conclude that sap -D stimulates in vivo the lysosomal degradation of ceramide. (C) 1994 Academic Press, Inc.