Glycosphingolipides neutres des lignées lymphoblastoïdes de maladie de Fabry établies par transformation par virus Epstein‐Barr

Salvayre, Robert; Maret, Arlette; Nègre, Anne; Douste‐Blazy, Louis

doi:10.1111/j.1432-1033.1985.tb08721.x

Cited by 3 publications

(1 citation statement)

References 36 publications

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“…Our group has demonstrated the validity of such a cellular system for the study of Fabry disease [Salvayre et al, , 1985, Tay-Sachs disease [Salvayre et al, 1983], Sandhoff disease [Maret et al, 1985], Niemann-Pick disease [Levade et al, 1984] and Wolman disease [Nègre et al, 1984], and we report here our results about Gaucher LCL.…”

Section: Introductionsupporting

confidence: 52%

ß-Glucosidase Isoenzymes in Epstein-Barr Virus-Transformed Lymphoid Cell Lines from Normal Subjects and Patients with Type 1 Gaucher Disease

Maret¹,

Salvayre²,

Samadi³

et al. 1987

Enzyme

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Lymphoid cell lines (LCL) from 3 adult patients with non-neuropathic Gaucher disease were established by Epstein-Barr virus (EBV) transformation and were investigated from the view of enzymology. (1) Glucosylceramide-ß-glucosidase (GlcCer-ß-glucosidase) was present in soluble and particulate fraction of LCL from normal subjects and was deficient in type 1 Gaucher LCL; the deficiency of all molecular forms, shown by electrofocusing, indicates that they are coded by the same gene. (2) The existence of two non-specific ßglucosidases, one soluble (minor), the other membrane-bound (major), was demonstrated in leucocytes and LCL from normals; in Gaucher LCL, these were also present in a normal range. (3) Characteristic properties of the non-specific membrane-bound ß-glucosidase were defined: lability at acidic pH and strong inhibitory effect by detergents. These properties allowed to discriminate it from the lysosomal GlcCer-ß-glucosidase and to define optimal assay conditions for determination of residual GlcCer-ß-glucosidase activity in Gaucher disease, using artificial substrate, without interference of non-specific membrane-bound ß-glucosidase. These results demonstrate that EBV-transformed LCL represent an accurate model system for enzymatic studies of Gaucher disease.

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Section: Introductionsupporting

confidence: 52%

ß-Glucosidase Isoenzymes in Epstein-Barr Virus-Transformed Lymphoid Cell Lines from Normal Subjects and Patients with Type 1 Gaucher Disease

Maret¹,

Salvayre²,

Samadi³

et al. 1987

Enzyme

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Biochemical diagnosis of Hunter syndrome on Epstein-Barr virus-transformed lymphoblastoid cell lines

Morabito

Giambarrasi

Rocchi

et al. 1989

Clinica Chimica Acta

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Extracellular origin of the lipid lysosomal storage in cultured fibroblasts from Wolman's disease

Salvayre

Nègre

Maret

et al. 1987

European Journal of Biochemistry

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The experiments reported here allowed us to compare the metabolism of neutral lipids from extracellular origin (lipoproteins) and endogenous origin (triacylglycerol biosynthesis induced by feeding cells with high levels of free fatty acid) in normal and acid-lipase-deficient fibroblasts (Wolman's disease). When the cells were grown in hyperlipemic-rich medium, a major neutral Iipid storage appeared in normal as well as in acid-lipase-deficient cells; this storage disappeared rapidly in normal cells during the 'chase', whereas in Wolman cells, the storage of cholesteryl esters and triacylglycerols remained unchanged, or only decreased very slowly. When the cells were fed with high levels of radiolabelled oleic acid, a major accumulation of radiolabelled triacylglycerols was observed. These cytoplasmic triacylglycerols were similarly degraded in normal and Wolman fibroblasts during the 'chase' period. From these results it was concluded that the neutral lipids stored in lysosomes of Wolman fibroblasts are only of extracellular origin (lipoproteins), whereas triacylglycerols biosynthesized by the cells do not participate in this accumulation. Therefore, both cellular compartments involved in triacylglycerol metabolism (lysosomes containing exogenous lipids and cytoplasmic granules of endogenously biosynthesized triacylglycerols) are strictly independent.Wolman's disease is an inherited lysosomal storage disorder characterized by a massive accumulation of triacylglycerols and cholesteryl esters in the tissues caused by a severe deficiency in lysosomal acid lipase activity [l -61. Theoretically, the stored neutral lipids can be of extracellular origin (lipoproteins) or from endogenous cellular biosynthesis. The exogenous lipoproteins taken up by the cells via a receptor-mediated or a receptor-independent endocytosis [7, 81 reach an endosomal compartment which fuses in part with the lysosomes [9, 101. On the other hand, the endogenous synthesis of triacylglycerols and cholesteryl esters is well known: cholesterol synthesized de novo by the cells, or liberated from the lysosomal compartment can be esterified by the cellular acyl-CoA: cholesterol acyltransferase [l 1, 121. The cytoplasmic triacylglycerol synthesis (through the phosphatidic acid pathway) is considerably increased when the cells receive a large influx of fatty acid which can induce a major cytoplasmic triacylglycerol storage [I3 -171. The relations between this cytoplasmic compartment containing endogenously synthesized triacylglycerols and the lysosomal compartment are poorly understood but some hypotheses have been formulated concerning the role of acid lysosomal lipase in the resorption of the cytoplasmic-induced triacylglycerol lipidosis [18].We report in this paper experimental data supporting the hypothesis that the neutral lipids accumulated in lysosomes of cultured fibroblasts from Wolman's disease (compared to normal) are mainly from exogenous (lipoprotein) origin, whereas endogenously synthesized neutral lipids do not parCorrespondence to R.

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Glycosphingolipides neutres des lignées lymphoblastoïdes de maladie de Fabry établies par transformation par virus Epstein‐Barr

Cited by 3 publications

References 36 publications

ß-Glucosidase Isoenzymes in Epstein-Barr Virus-Transformed Lymphoid Cell Lines from Normal Subjects and Patients with Type 1 Gaucher Disease

ß-Glucosidase Isoenzymes in Epstein-Barr Virus-Transformed Lymphoid Cell Lines from Normal Subjects and Patients with Type 1 Gaucher Disease

Biochemical diagnosis of Hunter syndrome on Epstein-Barr virus-transformed lymphoblastoid cell lines

Extracellular origin of the lipid lysosomal storage in cultured fibroblasts from Wolman's disease

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