Biliary excretion of glycolipid in induced or inherited glucosylceramide lipidosis

Pentchev, Peter G.; Gal, Andrew E.; Wong, Renee; Morrone, Stefania; Neumeyer, B.; Massey, Janice M.; Kanter, Robert A.; Sawitsky, Arthur; Brady, Roscoe O.

doi:10.1016/0005-2760(81)90279-4

Cited by 17 publications

(6 citation statements)

References 6 publications

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“…Each animal was intravenously (i.v.) injected in the tail, between 08:00 and 10:00 h, without anaesthesia with (i) labelled GMl dissolved in 0.1 ml of sterile physiological solution (Ghidoni et al, 1986); the total radioactivity injected was 50,Ci for [Sph-3H]GMl and 2.5 ,Ci for [stearoyl-'4C]GMl (both accounting for about 50 nmol of GM1); ii) 0.1 ml of a dispersion freshly prepared as described by Pentchev et al (1981), containing 50 ,Ci of radioactive GlcCer; (iii) 0.1 ml of a dispersion freshly prepared by the method of Soriano et al (1983), containing 50,uCi of radioactive GalCer or LacCer. In these forms of administration both gangliosides and neutral glycosphingolipids have previously been reported to be actively incorporated and metabolized in the liver, with a main role being played by the parenchymal cells (Pentchev et al, Soriano et al, 1983;Grosse et al, 1984;Tokoro et al, 1987).…”

Section: Animals and Animal Treatmentmentioning

confidence: 99%

Recycling of glucosylceramide and sphingosine for the biosynthesis of gangliosides and sphingomyelin in rat liver

Trinchera

Ghidoni

Sonnino

et al. 1990

Biochemical Journal

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It was previously shown that sphingomyelin and gangliosides can be biosynthesized starting from sphingosine or sphingosine-containing fragments which originated in the course of GM1 ganglioside catabolism. In the present paper we investigated which fragments were specifically re-used for sphingomyelin and ganglioside biosynthesis in rat liver. At 30 h after intravenous injection of GM1 labelled at the level of the fatty acid ([stearoyl-14C]GM1) or of the sphingosine ([Sph-3H]) moiety, it was observed that radioactive sphingomyelin was formed almost exclusively after the sphingosine-labelled-GM1 administration. This permitted the recognition of sphingosine as the metabolite re-used for sphingomyelin biosynthesis. Conversely, gangliosides more complex than GM1 were similarly radiolabelled after the two treatments, thus ruling out sphingosine re-utilization for ganglioside biosynthesis. For the identification of the lipid fragment re-used for ganglioside biosynthesis, we administered to rats neutral glycosphingolipids (galactosylceramide, glucosylceramide and lactosylceramide) each radiolabelled in the sphingosine moiety or in the terminal sugar residue. Thereafter we compared the formation of radiolabelled gangliosides in the liver with respect to the species administered and the label location. After galactosylceramide was injected, no radiolabelled gangliosides were formed. After the administration of differently labelled glucosylceramide, radiolabelled gangliosides were formed, regardless of the position of the label. After lactosylceramide administration, the ganglioside fraction became more radioactive when the long-chain-base-labelled precursors were used. These results suggest that glucosylceramide, derived from glycosphingolipid and ganglioside catabolism, is recycled for ganglioside biosynthesis.

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Section: Animals and Animal Treatmentmentioning

confidence: 99%

Recycling of glucosylceramide and sphingosine for the biosynthesis of gangliosides and sphingomyelin in rat liver

Trinchera

Ghidoni

Sonnino

et al. 1990

Biochemical Journal

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“…Presumably, the residual GCase activity is sufficient to hydrolyze endogenously generated GlcCer in parenchymal cells, but the storage material accumulates in the macrophages due to high turnover of exogenou s complex glycolipids arising from senescent cell membranes (Beutler 2001). It has been suggested that GlcCer does not accumulate overtly in hepatocytes due to efficient biliary secretion of GlcCer (Pentchev et al 1981; Tokoro et al 1987). Whether the presence of glucosylceramide and related lipids alter bile lithogenicity is not known.…”

Section: Introductionmentioning

confidence: 99%

High incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease

Taddei

Dziura

Chen

et al. 2010

J of Inher Metab Disea

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“…Furthermore, exogenously administered neutral glycosphingolipids are also taken up by cells and tissues and metabolized (Pentchev et al, 1981;Saito & Rosenberg, 1985;Chatterjee et al, 1986;Datta et al, 1986); in particular, liposomes containing lactosyl-ceramide (LacCer) have been reported to be actively incorporated by hepatocytes in vivo (Soriano et al, 1983;Grosse et al, 1984). On this basis, to study the mechanisms of ganglioside biosynthesis and transport, we intravenously administered a liposomal dispersion of radiolabelled LacCer to rats and then monitored the time course of the individual gangliosides which became radioactive in the Golgi-apparatus and plasma-membrane fractions prepared from the liver.…”

Section: Introductionmentioning

confidence: 99%

Subcellular biosynthesis and transport of gangliosides formed from exogenous lactosylceramide in rat liver

Trinchera

Ghidoni

1990

Biochemical Journal

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In order to clarify the mechanisms of ganglioside biosynthesis and transport we intravenously administered a liposomal dispersion of radiolabelled lactosylceramide (LacCer) to rats and then followed the time course of the individual gangliosides which became radioactive in the Golgi-apparatus and plasma-membrane fractions prepared from the liver. After administration of radiolabelled LacCer the liver retained a substantial amount of radioactivity, which was distributed among an organic phase (mainly residual LacCer), a fraction containing low-Mr substances (mainly 3H2O) and a ganglioside fraction. The hepatocytes were found to provide the bulk of gangliosides biosynthesized from exogenous LacCer. After subcellular fractionation, the total radioactive gangliosides increased in the Golgi apparatus up to 8 h, to then decrease and practically disappear at 24 h; in the plasma membranes they were progressively concentrated, accounting for high absolute values. Ganglioside patterns were greatly modified with time in both the Golgi apparatus and plasma membrane, but without significant differences between them. Biosynthesis in the Golgi apparatus and accumulation in the plasma membrane of each individual ganglioside followed a precursor-product relationship. The obtained results indicated that once a ganglioside is biosynthesized in the Golgi apparatus, it is in part made available for translocation to the plasma membrane, which rapidly occurs, and is in part retained in the Golgi apparatus, where it acts as a precursor for the biosynthesis of more glycosylated gangliosides.

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Biliary excretion of glycolipid in induced or inherited glucosylceramide lipidosis

Cited by 17 publications

References 6 publications

Recycling of glucosylceramide and sphingosine for the biosynthesis of gangliosides and sphingomyelin in rat liver

Recycling of glucosylceramide and sphingosine for the biosynthesis of gangliosides and sphingomyelin in rat liver

High incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease

Subcellular biosynthesis and transport of gangliosides formed from exogenous lactosylceramide in rat liver

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