title: Uptake and metabolism of radiolabelled GM1-ganglioside in skin fibroblasts from controls and patients with GM1-gangliosidosis.
abstract: The uptake and metabolism of [3-3H-sphingosine]GM1-ganglioside was measured in cultured skin fibroblasts from controls and patients with infantile, juvenile and adult GM1-gangliosidosis. When dissolved in medium with phosphatidylserine, GM1-ganglioside was efficiently taken up by cultured skin fibroblasts and transferred into lysosomes. A linear increase in GM1-ganglioside endocytosis was shown with phosphatidylserine concentrations of up to 40 micrograms/ml. A pulse-chase study revealed that [3H]GM1-ganglioside was metabolized to GM2-ganglioside, GM3-ganglioside, ceramide dihexoside, ceramide monohexoside, ceramide and sphingosine. Sphingosine was recycled to sphingomyelin. In a 20-h pulse study, cell lines from patients with GM1-gangliosidosis of infantile, juvenile and adult types hydrolysed 2-5%, 20-44% and 54-58% of the total endocytosed GM1-ganglioside respectively. These values were lower than in control cells (64.17 +/- 5.43% (n = 10]. The hydrolysis rates of exogenous [3H]GM1-ganglioside in cultured fibroblasts from patients with various types of GM1-gangliosidosis closely reflected the clinical severity.
authors.affiliation: Department of Pediatrics, Osaka University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Midorikawa
authors.forename: K
authors.initials: K
authors.lastname: Inui
authors.forename: S
authors.initials: S
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Yabuuchi
authors.forename: K
authors.initials: K
authors.lastname: Ogura
authors.forename: S
authors.initials: S
authors.lastname: Handa
mesh_terms: D002478:Cells, Cultured; D004705:Endocytosis; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005677:G(M1) Ganglioside / Q000378:metabolism*; D016537:Gangliosidosis, GM1 / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism; D010718:Phosphatidylserines / Q000494:pharmacology; D012867:Skin; D014316:Tritium
chemical_list: D010718:Phosphatidylserines; D014316:Tritium; D005677:G(M1) Ganglioside