Abstract
| Original language | English |
|---|---|
| Article number | 7 |
| Pages (from-to) | 16-27 |
| Number of pages | 12 |
| Journal | The Open Pathology Journal |
| Volume | 7 |
| Early online date | 6 Sep 2013 |
| DOIs | |
| Publication status | Published - 6 Sep 2013 |
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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.
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Activation of Sterol-Responsive Element Binding Proteins in a Sucrose-Induced Model of Lysosomal Storage. / Van Beersel, Guillaume; Jadot, Michel; Hamer, Isabelle; Arnould, Thierry.
In: The Open Pathology Journal, Vol. 7, 7, 06.09.2013, p. 16-27.Research output: Contribution to journal › Article
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 -