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

Research output: Contribution to journalArticle

77 Downloads (Pure)

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

    Fingerprint

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