Article (Scientific journals)
Metabolic reprogramming in transformed mouse cortical astrocytes: a proteomic study.
Bentaib, Azeddine; De Tullio, Pascal; Chneiweiss, Herve et al.
2015In Journal of Proteomics, 113, p. 292-314
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Keywords :
2D-DIGE; Warburg effect; cancerous transformation; glia; glioblastoma; glycolysis
Abstract :
[en] Metabolic reprogramming is thought to play a key role in sustaining the survival and proliferation of cancer cells. These changes facilitate for example the uptake and release of nutrients required for nucleotide, protein and lipid synthesis necessary for macromolecule assembly and tumor growth. We applied a 2D-DIGE (Two-Dimensional Differential in-Gel Electrophoresis) quantitative proteomic analysis to characterize the proteomes of mouse astrocytes that underwent in vitro cancerous transformation, and of their normal counterparts. Metabolic reprogramming effects on enzymatic and structural protein expression as well as associated metabolites abundance were quantified. Using enzymatic activity measurements and zymography, we documented and confirmed several changes in abundance and activity of various isoenzymes likely to participate in metabolic reprogramming. We found that after transformation, the cells increase their expression of glycolytic enzymes, thus augmenting their ability to use aerobic glycolysis (Warburg effect). An increased capacity to dispose of reducing equivalents through lactate production was also documented. Major effects on carbohydrates, amino acids and nucleotides metabolic enzymes were also observed. Conversely, the transformed cells reduced their enzymatic capacity for reactions of tricarboxylic acid oxidation, for neurotransmitter (glutamate) metabolism, for oxidative stress defense and their expression of astroglial markers. BIOLOGICAL SIGNIFICANCE: The use of a global approach based on a 2D DIGE analysis allows obtaining a comprehensive view of the metabolic reprogramming undergone by astrocytes upon cancerous transformation. Indeed, except for a few enzymes such as pyruvate carboxylase and glutaminase that were not detected in our initial analysis, pertinent information on the abundance of most enzymes belonging to pathways relevant to metabolic reprogramming was directly obtained. In this in vitro model, transformation causes major losses of astrocyte-specific proteins and functions and the acquisition of metabolic adaptations that favor intermediate metabolites production for increased macromolecule biosynthesis. Thus our approach appears to be readily applicable for the investigation of changes in protein abundance that determine various transformed cell phenotypes. It could similarly be applied to the evaluation of the effects of treatments aimed at correcting the consequences of cell transformation.
Disciplines :
Oncology
Biochemistry, biophysics & molecular biology
Author, co-author :
Bentaib, Azeddine;  Université de Liège - ULiège > GIGA-Neurosciences
De Tullio, Pascal ;  Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Chneiweiss, Herve;  Université Pierre et Marie Curie > Plasticité Gliale et Tumeurs cérébrales > UMR8246 CNRS/U1130 Inserm/ UMCR18
Hermans, Emmanuel;  Université Catholique de Louvain > Institute of Neurosciences > Group of Neuropharmacology
Junier, Marie-Pierre;  Université Pierre et Marie Curie > Plasticité Gliale et Tumeurs cérébrales > UMR8246 CNRS/U1130 Inserm/ UMCR18
Leprince, Pierre ;  Université de Liège - ULiège > GIGA - Neurosciences
Language :
English
Title :
Metabolic reprogramming in transformed mouse cortical astrocytes: a proteomic study.
Publication date :
January 2015
Journal title :
Journal of Proteomics
ISSN :
1874-3919
eISSN :
1876-7737
Publisher :
Elsevier, Netherlands
Volume :
113
Pages :
292-314
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
ARC "Glyvir"
Fonds Léon Fredericq [BE]
FRSM - Fonds de la Recherche Scientifique Médicale [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Commentary :
Copyright (c) 2014. Published by Elsevier B.V.
Available on ORBi :
since 16 October 2014

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