Activation of Sterol-Responsive Element Binding Proteins in a Sucrose-Induced Model of Lysosomal Storage

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Abstract

Abstract: The accumulation of pinocytosed sucrose in lysosomes constitutes a convenient mean to mimic a lysosomal storage and to study how such storage impacts the biology of the organelle and beyond. Several reports have shown that lysosomal storages can perturb the redistribution of lysosomal lipids, cholesterol in particular. Our goal was to analyse the effect of the intralysosomal accumulation of sucrose on the transcription factors Sterol Regulatory Element Binding Proteins (SREBPs): key actors of the regulation of lipid metabolism. We show that 143B cells grown in the presence of sucrose present a modified distribution of non-esterified cholesterol, which is associated with an increase in the activity of SREBPs. The activation of these transcription factors is associated with an increase in the expression of some of their target genes: HMG-CoA synthase and mevalonate kinase, and with an increase in total lipid biosynthesis. Finally, using siRNA interference we demonstrate that SREBP-2 but not SREBP-1a is responsible for the increase in the expression of the genes encoding these two enzymes.
Original languageEnglish
Article number7
Pages (from-to)16-27
Number of pages12
JournalThe Open Pathology Journal
Volume7
Early online date6 Sep 2013
DOIs
Publication statusPublished - 6 Sep 2013

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Sterols
Sterol Regulatory Element Binding Proteins
Sucrose
Carrier Proteins
mevalonate kinase
Hydroxymethylglutaryl-CoA Synthase
Sterol Regulatory Element Binding Protein 2
Transcription Factors
Cholesterol
Sterol Regulatory Element Binding Protein 1
Pinocytosis
Lipids
Lysosomes
Lipid Metabolism
Organelles
Small Interfering RNA
Gene Expression
Enzymes
Genes

Keywords

  • FASN: fatty acid synthase, HMG-CoA synthase: 3-hydroxy-3-methylglutaryl- Coenzyme A synthase, LDLr: low density lipoprotein receptor, LSDs: lysosomal storage diseases, microtubule-associated protein 1-light chain 3 beta: MAP1-LC3beta/LC3, MVK: mevalonate kinase, SCD-1/2: stearoyl-CoA desaturase 1/2, SREBPs: Sterol Regulatory Element Binding Proteins.

Cite this

@article{a0fb6eaf6d2b41a29015ba6a354f3de3,
title = "Activation of Sterol-Responsive Element Binding Proteins in a Sucrose-Induced Model of Lysosomal Storage",
abstract = "Abstract: The accumulation of pinocytosed sucrose in lysosomes constitutes a convenient mean to mimic a lysosomal storage and to study how such storage impacts the biology of the organelle and beyond. Several reports have shown that lysosomal storages can perturb the redistribution of lysosomal lipids, cholesterol in particular. Our goal was to analyse the effect of the intralysosomal accumulation of sucrose on the transcription factors Sterol Regulatory Element Binding Proteins (SREBPs): key actors of the regulation of lipid metabolism. We show that 143B cells grown in the presence of sucrose present a modified distribution of non-esterified cholesterol, which is associated with an increase in the activity of SREBPs. The activation of these transcription factors is associated with an increase in the expression of some of their target genes: HMG-CoA synthase and mevalonate kinase, and with an increase in total lipid biosynthesis. Finally, using siRNA interference we demonstrate that SREBP-2 but not SREBP-1a is responsible for the increase in the expression of the genes encoding these two enzymes.",
keywords = "FASN: fatty acid synthase, HMG-CoA synthase: 3-hydroxy-3-methylglutaryl- Coenzyme A synthase, LDLr: low density lipoprotein receptor, LSDs: lysosomal storage diseases, microtubule-associated protein 1-light chain 3 beta: MAP1-LC3beta/LC3, MVK: mevalonate kinase, SCD-1/2: stearoyl-CoA desaturase 1/2, SREBPs: Sterol Regulatory Element Binding Proteins.",
author = "{Van Beersel}, Guillaume and Michel Jadot and Isabelle Hamer and Thierry Arnould",
year = "2013",
month = "9",
day = "6",
doi = "DOI: 10.2174/1874375720130905003",
language = "English",
volume = "7",
pages = "16--27",
journal = "The Open Pathology Journal",
issn = "1874-3757",

}

TY - JOUR

T1 - Activation of Sterol-Responsive Element Binding Proteins in a Sucrose-Induced Model of Lysosomal Storage

AU - Van Beersel, Guillaume

AU - Jadot, Michel

AU - Hamer, Isabelle

AU - Arnould, Thierry

PY - 2013/9/6

Y1 - 2013/9/6

N2 - Abstract: The accumulation of pinocytosed sucrose in lysosomes constitutes a convenient mean to mimic a lysosomal storage and to study how such storage impacts the biology of the organelle and beyond. Several reports have shown that lysosomal storages can perturb the redistribution of lysosomal lipids, cholesterol in particular. Our goal was to analyse the effect of the intralysosomal accumulation of sucrose on the transcription factors Sterol Regulatory Element Binding Proteins (SREBPs): key actors of the regulation of lipid metabolism. We show that 143B cells grown in the presence of sucrose present a modified distribution of non-esterified cholesterol, which is associated with an increase in the activity of SREBPs. The activation of these transcription factors is associated with an increase in the expression of some of their target genes: HMG-CoA synthase and mevalonate kinase, and with an increase in total lipid biosynthesis. Finally, using siRNA interference we demonstrate that SREBP-2 but not SREBP-1a is responsible for the increase in the expression of the genes encoding these two enzymes.

AB - Abstract: The accumulation of pinocytosed sucrose in lysosomes constitutes a convenient mean to mimic a lysosomal storage and to study how such storage impacts the biology of the organelle and beyond. Several reports have shown that lysosomal storages can perturb the redistribution of lysosomal lipids, cholesterol in particular. Our goal was to analyse the effect of the intralysosomal accumulation of sucrose on the transcription factors Sterol Regulatory Element Binding Proteins (SREBPs): key actors of the regulation of lipid metabolism. We show that 143B cells grown in the presence of sucrose present a modified distribution of non-esterified cholesterol, which is associated with an increase in the activity of SREBPs. The activation of these transcription factors is associated with an increase in the expression of some of their target genes: HMG-CoA synthase and mevalonate kinase, and with an increase in total lipid biosynthesis. Finally, using siRNA interference we demonstrate that SREBP-2 but not SREBP-1a is responsible for the increase in the expression of the genes encoding these two enzymes.

KW - FASN: fatty acid synthase, HMG-CoA synthase: 3-hydroxy-3-methylglutaryl- Coenzyme A synthase, LDLr: low density lipoprotein receptor, LSDs: lysosomal storage diseases, microtubule-associated protein 1-light chain 3 beta: MAP1-LC3beta/LC3, MVK: mevalonate

U2 - DOI: 10.2174/1874375720130905003

DO - DOI: 10.2174/1874375720130905003

M3 - Article

VL - 7

SP - 16

EP - 27

JO - The Open Pathology Journal

JF - The Open Pathology Journal

SN - 1874-3757

M1 - 7

ER -