Glycogen Metabolism as a Marker of Astrocyte Differentiation

Brunet, Jean-François; Allaman, Igor; Magistretti, Pierre J.; Pellerin, Luc

doi:10.1038/jcbfm.2009.207

Cited by 31 publications

(29 citation statements)

References 18 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Remarkably the sole knockdown of G6PC was able to decrease the aggressive phenotype of BTICs potentially through the down-regulation of the CD133/AKT axis and an increase in glycogen accumulation which has been previously shown to induce cell death in cancer cells if it is not properly metabolized (43, 44). Glycogen was recently identified as a marker of astrocytic differentiation (52). Interestingly, we also observed astrocytic differentiation along with glycogen accumulation in the shG6PC BTICs.…”

Section: Discussionmentioning

confidence: 99%

Glucose-6–phosphatase Is a Key Metabolic Regulator of Glioblastoma Invasion

Abbadi

Rodarte

Abutaleb

et al. 2014

Molecular Cancer Research

View full text Add to dashboard Cite

Glioblastoma (GBM) remains the most aggressive primary brain cancer in adults. Similar to other cancers, GBM cells undergo metabolic reprogramming to promote proliferation and survival. Glycolytic inhibition is widely used to target such reprogramming. However, the stability of glycolytic inhibition in GBM remains unclear especially in a hypoxic tumor microenvironment. In this study, it was determined that glucose-6-phosphatase-α (G6PC/G6Pase) expression is elevated in GBM when compared to normal brain. Human-derived brain tumor initiating cells (BTICs) utilize this enzyme to counteract glycolytic inhibition induced by 2-Deoxy-D-glucose (2DG) and sustain malignant progression. Down-regulation of G6PC renders the majority of these cells unable to survive glycolytic inhibition, and promotes glycogen accumulation through the activation of glycogen synthase (GYS1) and inhibition of glycogen phosphorylase (PYGL). Moreover, BTICs that survive G6PC knockdown are less aggressive (reduced migration, invasion, proliferation, and increased astrocytic differentiation). Collectively, these findings establish G6PC as a key enzyme with pro-malignant functional consequences that has not been previously reported in GBM and identify it as a potential therapeutic target.

show abstract

Section: Discussionmentioning

confidence: 99%

Glucose-6–phosphatase Is a Key Metabolic Regulator of Glioblastoma Invasion

Abbadi

Rodarte

Abutaleb

et al. 2014

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…22 We now demonstrate for the first time that human stem cell-derived astrocytes synthesize glycogen as well as markers associated with its metabolism, suggesting that these cells are well differentiated and resemble mature astrocytes. 32 Co-cultures also respond to neuromodulators and neuronal activity by enhancing glucose uptake as well as inducing glycogenesis and glycogenolysis. While postmitotic co-cultures derived from NT2.D1 cells are widely accepted as a model of the human CNS, some studies have suggested that NT2.NA resemble human fetal primary cells.…”

Section: Discussionmentioning

confidence: 99%

Functional Astrocyte-Neuron Lactate Shuttle in a Human Stem Cell-Derived Neuronal Network

Tarczyluk

Nagel

O’Neil

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

The NT2.D1 cell line is one of the most well-documented embryocarcinoma cell lines, and can be differentiated into neurons and astrocytes. Great focus has also been placed on defining the electrophysiological properties of the neuronal cells, and more recently we have investigated the functional properties of their associated astrocytes. We now show for the first time that human stem cellderived astrocytes produce glycogen and that co-cultures of these cells demonstrate a functional astrocyte-neuron lactate shuttle (ANLS). The ANLS hypothesis proposes that during neuronal activity, glutamate released into the synaptic cleft is taken up by astrocytes and triggers glucose uptake, which is converted into lactate and released via monocarboxylate transporters for neuronal use. Using mixed cultures of NT2-derived neurons and astrocytes, we have shown that these cells modulate their glucose uptake in response to glutamate. Additionally, we demonstrate that in response to increased neuronal activity and under hypoglycaemic conditions, co-cultures modulate glycogen turnover and increase lactate production. Similar results were also shown after treatment with glutamate, potassium, isoproterenol, and dbcAMP. Together, these results demonstrate for the first time a functional ANLS in a human stem cell-derived co-culture.

show abstract

“…Astrocytes possess a specific cytoarchitecture that enables them to sense their surroundings and dynamically respond to changes in their microenvironment, such as changes in the glucose levels [25,51]. Astrocytes take up glucose and characteristically display a high glycolytic rate [52,53]. C6 astroglial cells metabolize glucose in relation to their sensitivity to the changes in extracellular glucose levels [54][55][56][57].…”

Section: Introductionmentioning

confidence: 99%

Gliopreventive effects of guanosine against glucose deprivation in vitro

Quincozes‐Santos

Bobermin

Souza

et al. 2013

Purinergic Signalling

View full text Add to dashboard Cite

Guanosine, a guanine-based purine, is recognized as an extracellular signaling molecule that is released from astrocytes and confers neuroprotective effects in several in vivo and in vitro studies. Astrocytes regulate glucose metabolism, glutamate transport, and defense mechanism against oxidative stress. C6 astroglial cells are widely used as an astrocyte-like cell line to study the astrocytic function and signaling pathways. Our previous studies showed that guanosine modulates the glutamate uptake activity, thus avoiding glutamatergic excitotoxicity and protecting neural cells. The goal of this study was to determine the gliopreventive effects of guanosine against glucose deprivation in vitro in cultured C6 cells. Glucose deprivation induced cytotoxicity, an increase in reactive oxygen and nitrogen species (ROS/RNS) levels and lipid peroxidation as well as affected the metabolism of glutamate, which may impair important astrocytic functions. Guanosine prevented glucose deprivation-induced toxicity in C6 cells by modulating oxidative and nitrosative stress and glial responses, such as the glutamate uptake, the glutamine synthetase activity, and the glutathione levels. Glucose deprivation decreased the level of EAAC1, the main glutamate transporter present in C6 cells. Guanosine also prevented this effect, most likely through PKC, PI3K, p38 MAPK, and ERK signaling pathways. Taken together, these results show that guanosine may represent an important mechanism for protection of glial cells against glucose deprivation. Additionally, this study contributes to a more thorough understanding of the glial-and redox-related protective properties of guanosine in astroglial cells.

show abstract

Glycogen Metabolism as a Marker of Astrocyte Differentiation

Cited by 31 publications

References 18 publications

Glucose-6–phosphatase Is a Key Metabolic Regulator of Glioblastoma Invasion

Glucose-6–phosphatase Is a Key Metabolic Regulator of Glioblastoma Invasion

Functional Astrocyte-Neuron Lactate Shuttle in a Human Stem Cell-Derived Neuronal Network

Gliopreventive effects of guanosine against glucose deprivation in vitro

Contact Info

Product

Resources

About