Saposins (sap) A and C activate the degradation of galactosylceramide in living cells
| Autor: | Thierry Levade, Helen Christomanou, Masao Hiraiwa, Barbara C. Paton, Martine Chatelut, John S. O'Brien, Klaus Harzer |
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| Rok vydání: | 1997 |
| Předmět: |
Ceramide
Biophysics Galactosylceramides Simian virus 40 Biology Gangliosidosis Biochemistry Saposins Amidohydrolases Cell Line Sphingolipidoses Hydrolysis chemistry.chemical_compound Structural Biology In vivo Genetics medicine Ceramidases Humans Saposin C Fibroblast Saposin A Molecular Biology Cell Line Transformed Glycoproteins Skin Gangliosidosis GM1 Cell Biology Metabolism Fibroblasts medicine.disease In vitro Leukodystrophy Globoid Cell Lysosomal Storage Diseases medicine.anatomical_structure chemistry Cell culture β-Galactocerebrosidase Galactosylceramide |
| Zdroj: | FEBS letters. 417(3) |
| ISSN: | 0014-5793 |
| Popis: | In loading tests using galactosylceramide which had been labelled with tritium in the ceramide moiety, living skin fibroblast lines derived from the original prosaposin-deficient patients had a markedly reduced capacity to degrade galactosylceramide. The hydrolysis of galactosylceramide could be partially restored in these cells, up to about half the normal rate, by adding pure saposin A, pure saposin C, or a mixture of these saposins to the culture medium. By contrast, saposins B and D had little effect on galactosylceramide hydrolysis in the prosaposin-deficient cells. Cells from β-galactocerebrosidase-deficient (Krabbe) patients had a relatively high residual galactosylceramide degradation, which was similar to the rate observed for prosaposin-deficient cells in the presence of saposin A or C. An SV40-transformed fibroblast line from the original saposin C-deficient patient, where saposin A is not affected, showed normal degradation of galactosylceramide. The findings support the hypothesis, which was deduced originally from in vitro experiments, that saposins A and C are the in vivo activators of galactosylceramide degradation. Although the results with saposin C-deficient fibroblasts suggest that the presence of only saposin A allows galactosylceramide breakdown to proceed at a normal rate in fibroblasts, it remains to be determined whether saposins A and C can substitute for each other with respect to their effects on galactosylceramide metabolism in the whole organism. |
| Databáze: | OpenAIRE |
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