Premium
Uptake and metabolism of radiolabelled GM1‐ganglioside in skin fibroblasts from controls and patients with GM1‐gangliosidosis
Author(s) -
Midorikawa M.,
Inui K.,
Okada S.,
Yabuuchi H.,
Ogura K.,
Handa S.
Publication year - 1991
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf01799941
Subject(s) - ganglioside , ceramide , sphingomyelin , sphingosine , phosphatidylserine , biochemistry , gangliosidosis , biology , endocrinology , medicine , chemistry , enzyme , cholesterol , apoptosis , receptor , phospholipid , membrane
Summary The uptake and metabolism of [3‐ 3 H‐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 γ m/ml. A pulse‐chase study revealed that [ 3 H]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 [ 3 H]GM1‐ganglioside in cultured fibroblasts from patients with various types of GM1‐gangliosidosis closely reflected the clinical severity.