The effects of N-hexyl-O-glucosyl sphingosine on normal cultured human fibroblasts: a chemical model for Gaucher's disease.
Normal human skin fibroblasts were grown in the presence of N-hexyl-O-glucosyl sphingosine (HGS), an inhibitor of aryl glucosidase and glucocerebrosidase. Tests of the cells with aryl glycosides showed that beta-glucosidase activity in the cells was drastically reduced while other enzyme activities (alpha-glucosidase, beta-galactosidase, and N-acetyl-beta-hexosaminidase) were normal or elevated. Exposure of cells to HGS for 28 days resulted in increased values for cell weight per plate, glucocerebroside concentration, and galactosyl-galactosylglucosyl ceramide concentration. The concentrations of total lipid, cholesterol, and protein were unchanged, as was the fatty acid distribution within the glycolipids. Chemically, the inhibitor-treated cells exhibited a model form of Gaucher's disease. Although many membranous cytoplasmic inclusions were induced by HGS, they were unlike the characteristic inclusions seen in individuals with the genetic disorder. Skin fibroblasts from a Gaucher patient showed no abnormalities in composition or appearance.
D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects* / Q000648:ultrastructure; D005696:Galactosidases / Q000378:metabolism; D005776:Gaucher Disease; D005959:Glucosidases / Q000378:metabolism; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors; D006056:Golgi Apparatus / Q000648:ultrastructure; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D008854:Microscopy, Electron; D008954:Models, Biological; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D013110:Sphingosine / Q000494:pharmacology*
D010744:Phosphoric Monoester Hydrolases; D005696:Galactosidases; D005959:Glucosidases; D006596:Hexosaminidases; D005962:Glucosylceramidase; D013110:Sphingosine