Impairment of ganglioside metabolism in cultured fibroblasts from Salla patients

Marina Pitto, Vanna Chigorno, Martin Renlund, Guido Tettamanti

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The metabolic processing of sialoglycolipids (gangliosides) was investigated in cultures of skin fibroblasts obtained from two patients affected with Salla disease. Cultured fibroblasts were fed with GM1 ganglioside [3H]-radiolabelled at the sialic acid ([NeuAc-3H]GM1) or sphingosine ([Sph-3H]GMl) moiety. Formation of metabolites was followed in pulse-chase experiments. It was observed that: (a) Salla fibroblasts, fed with [NeuAc-3H]GM1 accumulate radioactive free sialic acid in the lysosomal compartment and show a much lower sialic acid re-cycling for biosynthetic purposes than control fibroblasts, as demonstrated by decreased incorporation of the label into glycolipids and glycoproteins; (b) Salla fibroblasts, fed with [NeuAc-3H]GM1 or [Sph-3H]GM1, tend to accumulate gangliosides GM2 andGM3, and to reduce the breakdown products following the desialosylation step, presumably as a consequence of the inhibition of sialidase by free sialic acid; (c) owing to (b) the basal production of the bioregulators of sphingoid nature, ceramide and sphingosine, is reduced, as well as re-cycling of these substances for biosynthetic purposes, with further reduction of the turnover rate of sphingolipids. The decreased turnover rate of sialoglycoconjugates and sphingolipids, together with the diminished formation of bioregulators of sphingoid nature, may play a relevant role in the pathogenesis of the disease.

Original languageEnglish
Pages (from-to)143-157
Number of pages15
JournalClinica Chimica Acta
Volume247
Issue number1-2
DOIs
Publication statusPublished - Mar 29 1996

Fingerprint

Gangliosides
Fibroblasts
Metabolism
N-Acetylneuraminic Acid
Sphingolipids
Sphingosine
Recycling
Sialic Acid Storage Disease
G(M2) Ganglioside
G(M1) Ganglioside
Ceramides
Glycolipids
Neuraminidase
Metabolites
Cell culture
Labels
Glycoproteins
Skin
Processing
Experiments

Keywords

  • cultured fibroblast
  • ganglioside metabolism
  • Salla disease
  • sialic acid

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

Cite this

Impairment of ganglioside metabolism in cultured fibroblasts from Salla patients. / Pitto, Marina; Chigorno, Vanna; Renlund, Martin; Tettamanti, Guido.

In: Clinica Chimica Acta, Vol. 247, No. 1-2, 29.03.1996, p. 143-157.

Research output: Contribution to journalArticle

Pitto, Marina ; Chigorno, Vanna ; Renlund, Martin ; Tettamanti, Guido. / Impairment of ganglioside metabolism in cultured fibroblasts from Salla patients. In: Clinica Chimica Acta. 1996 ; Vol. 247, No. 1-2. pp. 143-157.
@article{d25c6a30b5014e9fbe7fca278cc91af7,
title = "Impairment of ganglioside metabolism in cultured fibroblasts from Salla patients",
abstract = "The metabolic processing of sialoglycolipids (gangliosides) was investigated in cultures of skin fibroblasts obtained from two patients affected with Salla disease. Cultured fibroblasts were fed with GM1 ganglioside [3H]-radiolabelled at the sialic acid ([NeuAc-3H]GM1) or sphingosine ([Sph-3H]GMl) moiety. Formation of metabolites was followed in pulse-chase experiments. It was observed that: (a) Salla fibroblasts, fed with [NeuAc-3H]GM1 accumulate radioactive free sialic acid in the lysosomal compartment and show a much lower sialic acid re-cycling for biosynthetic purposes than control fibroblasts, as demonstrated by decreased incorporation of the label into glycolipids and glycoproteins; (b) Salla fibroblasts, fed with [NeuAc-3H]GM1 or [Sph-3H]GM1, tend to accumulate gangliosides GM2 andGM3, and to reduce the breakdown products following the desialosylation step, presumably as a consequence of the inhibition of sialidase by free sialic acid; (c) owing to (b) the basal production of the bioregulators of sphingoid nature, ceramide and sphingosine, is reduced, as well as re-cycling of these substances for biosynthetic purposes, with further reduction of the turnover rate of sphingolipids. The decreased turnover rate of sialoglycoconjugates and sphingolipids, together with the diminished formation of bioregulators of sphingoid nature, may play a relevant role in the pathogenesis of the disease.",
keywords = "cultured fibroblast, ganglioside metabolism, Salla disease, sialic acid",
author = "Marina Pitto and Vanna Chigorno and Martin Renlund and Guido Tettamanti",
year = "1996",
month = "3",
day = "29",
doi = "10.1016/0009-8981(95)06243-2",
language = "English",
volume = "247",
pages = "143--157",
journal = "Clinica Chimica Acta",
issn = "0009-8981",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Impairment of ganglioside metabolism in cultured fibroblasts from Salla patients

AU - Pitto, Marina

AU - Chigorno, Vanna

AU - Renlund, Martin

AU - Tettamanti, Guido

PY - 1996/3/29

Y1 - 1996/3/29

N2 - The metabolic processing of sialoglycolipids (gangliosides) was investigated in cultures of skin fibroblasts obtained from two patients affected with Salla disease. Cultured fibroblasts were fed with GM1 ganglioside [3H]-radiolabelled at the sialic acid ([NeuAc-3H]GM1) or sphingosine ([Sph-3H]GMl) moiety. Formation of metabolites was followed in pulse-chase experiments. It was observed that: (a) Salla fibroblasts, fed with [NeuAc-3H]GM1 accumulate radioactive free sialic acid in the lysosomal compartment and show a much lower sialic acid re-cycling for biosynthetic purposes than control fibroblasts, as demonstrated by decreased incorporation of the label into glycolipids and glycoproteins; (b) Salla fibroblasts, fed with [NeuAc-3H]GM1 or [Sph-3H]GM1, tend to accumulate gangliosides GM2 andGM3, and to reduce the breakdown products following the desialosylation step, presumably as a consequence of the inhibition of sialidase by free sialic acid; (c) owing to (b) the basal production of the bioregulators of sphingoid nature, ceramide and sphingosine, is reduced, as well as re-cycling of these substances for biosynthetic purposes, with further reduction of the turnover rate of sphingolipids. The decreased turnover rate of sialoglycoconjugates and sphingolipids, together with the diminished formation of bioregulators of sphingoid nature, may play a relevant role in the pathogenesis of the disease.

AB - The metabolic processing of sialoglycolipids (gangliosides) was investigated in cultures of skin fibroblasts obtained from two patients affected with Salla disease. Cultured fibroblasts were fed with GM1 ganglioside [3H]-radiolabelled at the sialic acid ([NeuAc-3H]GM1) or sphingosine ([Sph-3H]GMl) moiety. Formation of metabolites was followed in pulse-chase experiments. It was observed that: (a) Salla fibroblasts, fed with [NeuAc-3H]GM1 accumulate radioactive free sialic acid in the lysosomal compartment and show a much lower sialic acid re-cycling for biosynthetic purposes than control fibroblasts, as demonstrated by decreased incorporation of the label into glycolipids and glycoproteins; (b) Salla fibroblasts, fed with [NeuAc-3H]GM1 or [Sph-3H]GM1, tend to accumulate gangliosides GM2 andGM3, and to reduce the breakdown products following the desialosylation step, presumably as a consequence of the inhibition of sialidase by free sialic acid; (c) owing to (b) the basal production of the bioregulators of sphingoid nature, ceramide and sphingosine, is reduced, as well as re-cycling of these substances for biosynthetic purposes, with further reduction of the turnover rate of sphingolipids. The decreased turnover rate of sialoglycoconjugates and sphingolipids, together with the diminished formation of bioregulators of sphingoid nature, may play a relevant role in the pathogenesis of the disease.

KW - cultured fibroblast

KW - ganglioside metabolism

KW - Salla disease

KW - sialic acid

UR - http://www.scopus.com/inward/record.url?scp=0029940662&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029940662&partnerID=8YFLogxK

U2 - 10.1016/0009-8981(95)06243-2

DO - 10.1016/0009-8981(95)06243-2

M3 - Article

VL - 247

SP - 143

EP - 157

JO - Clinica Chimica Acta

JF - Clinica Chimica Acta

SN - 0009-8981

IS - 1-2

ER -