Modulation of astrocytic metabolic phenotype by proinflammatory cytokines

Détails

ID Serval
serval:BIB_3D444977EB7C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Modulation of astrocytic metabolic phenotype by proinflammatory cytokines
Périodique
Glia
Auteur⸱e⸱s
Gavillet M., Allaman I., Magistretti P.J.
ISSN
1098-1136
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
56
Numéro
9
Pages
975-989
Langue
anglais
Résumé
Astrocytes play an important role in nervous system homeostasis. In particular, they contribute to the regulation of local energy metabolism and to oxidative stress defence. In previous experiments, we showed that long-term treatment with interleukin 1alpha (IL-1alpha) or tumor necrosis factor-alpha (TNFalpha) alone increases glucose utilization in primary culture of mouse astrocytes. In our study, we report that a combination of IL-1beta and TNFalpha exerts a synergistic effect on glucose utilization and markedly modifies the metabolic phenotype of astrocytes. Thus, IL-1beta+TNFalpha treated astrocytes show a marked decrease in glycogen levels, a slight but not significant decrease in lactate release as well as a massive increase in both the pentose phosphate pathway and TCA cycle activities. Glutamate-stimulated glucose utilization and lactate release, a typical feature of astrocyte energy metabolism, are altered after pretreatment with IL-1beta+TNFalpha. As far as mechanisms for oxidative stress defence are concerned, we observed that treatment with IL-1beta+TNFalpha decreases cellular glutathione content and increases glutathione release into the extracellular space while stimulating superoxide anion and nitric oxide production as well as H(2)O(2) release. Interestingly, stimulation of glucose utilization by IL-1beta+TNFalpha is not affected by the antioxidant N-acetyl-L-cysteine, suggesting that cellular stress does not account for this effect. Finally, the effects of cytokines on glucose utilization appear to involve multiple signaling cascades including the phosphoinositide 3-kinase and mitogen-activated protein kinases. Taken together these results establish that a proinflammatory environment such as observed in several neuropathological conditions including Alzheimer's disease, markedly modifies the metabolic phenotype of astrocytes.
Mots-clé
Animals, Astrocytes, Cells, Cultured, Cytokines, Energy Metabolism, Glucose, Glutamates, Glycolysis, Inflammation Mediators, Mice, Phenotype
Pubmed
Web of science
Création de la notice
13/06/2008 15:48
Dernière modification de la notice
20/08/2019 13:33
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