Metabolic Processing of Gangliosides by Normal and Salla Human Fibroblasts in Culture
Journal of Biological Chemistry, ISSN: 0021-9258, Vol: 271, Issue: 36, Page: 21738-21744
1996
- 36Citations
- 13Captures
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Metrics Details
- Citations36
- Citation Indexes36
- 36
- CrossRef26
- Captures13
- Readers13
Article Description
Cultured fibroblasts from normal subjects and from subjects affected by Salla disease, characterized by the lack or misfunction of the membrane carrier responsible for the egress of sialic acid from lysosomes, were fed with ganglioside G M3 labeled at the sialic acid acetyl group, [ Neu5Ac - 3 H]G M3, or at C-3 of sphingosine (Sph), [ Sph - 3 H]G M3, or at C-1 of stearoyl chain, [ stearoyl - 14 C]G M3. After a 15-h pulse the total amount of cell-bound G M3 corresponded to about 2% of the endogenous ganglioside content. Cells were then subjected to a 72-h chase, and the radioactive products from both ganglioside catabolism and salvage processes of catabolic fragments were measured. These data indicated that about 50% of the cell-bound ganglioside underwent metabolic processing, suggesting a ganglioside half-life of 2-3 days. [ Neu5Ac - 3 H] formed from [ Neu5Ac - 3 H]G M3 degradation was mostly re-cycled for the biosynthesis of gangliosides and sialoglycoproteins, only a minor part being degraded to [ 3 H]water, which constituted only 1.6% of total metabolite linked radioactivity. [ Sph - 3 H] from the [ Sph - 3 H]G M3 degradation was partly re-cycled for the biosynthesis of gangliosides, neutral glycosphingolipids and sphingomyelin, and partly (about 20% of the total metabolite linked radioactivity) degraded to [ 3 H]water. In Salla fibroblasts metabolic processing of [ Neu5Ac - 3 H]G M3 produced large amounts of free [ 3 H]Neu5Ac, and a reduced incorporation of radioactivity into glycoconjugates (as compared to normal cells). However, the accumulation of free Neu5Ac was not accompanied by an increase of tritiated water. LacCer and Cer from [ stearoyl - 14 C]G M3 catabolism were found to accumulate in Salla fibroblasts, an indication that the enzymes of glycosphingolipid metabolism were affected by the impairment of Neu5Ac egress from lysosomes. Particularly relevant was the accumulation of ceramide which was hardly detectable in control cells.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0021925819618533; http://dx.doi.org/10.1074/jbc.271.36.21738; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0029786969&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/8702969; https://linkinghub.elsevier.com/retrieve/pii/S0021925819618533; https://dx.doi.org/10.1074/jbc.271.36.21738
Elsevier BV
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