glycogen and Glioma

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Aerobiosis; Anaerobiosis; Animals; Brain; Brain Neoplasms; Creatine; Ependymoma; Glioma; Glucose; Glycogen; Glycolysis; Humans; Hypoxia; Ischemia; Lactates; Meningioma; Mice; Neoplasms, Experimental; Neurilemmoma; Oxygen Consumption; Periodic Acid; Phosphofructokinase-1; Phosphorus; RNA; Vestibulocochlear Nerve

According to the cancer stem cell theory malignant glioma is incurable because of the presence of the cancer stem cells - a subpopulation of cells that are resistant to therapy and cause the recurrence of a tumor after surgical resection. Several protein markers of cancer stem cell were reported but none of those is fully reliable to grade the content of stem cells in a tumor. Hereby we propose Fourier transform infrared (FTIR) microspectroscopy as an alternative, labelfree, non-damaging and fast method to identify glioma stem cells based on their own spectral characteristics. The analysis of FTIR data revealed that in NCH421k cells, a model of glioma stem cells, the relative content of lipids is higher than in their all-trans retinoic acid-differentiated counterparts. Moreover, it has been assessed that stem cells have more rigid cellular membranes and more phosphorylated proteins, whereas after differentiation glycogen level increases. The ability of FTIR to estimate the content of stem cells in a heterogeneous sample, on the base of the identified spectral markers, and to classify stem and non-stem cells into two separate populations was probed. Although it was not possible to calculate the exact percentage of each subpopulation, we could clearly see that with the increasing amount of differentiated cells in a sample, more hits occupy the PC space previously identified as a space of differentiated cells. The present study is therefore an initial step towards the development of a FTIR based protocol in clinical practice to estimate the content of stem cells in a tumor sample.

Topics: AC133 Antigen; Antigens, CD; Apoptosis; Cell Differentiation; Cell Line, Tumor; Glioma; Glycogen; Glycoproteins; Humans; Microscopy, Fluorescence; Neoplastic Stem Cells; Peptides; Principal Component Analysis; Spectroscopy, Fourier Transform Infrared; Tretinoin

The present work was undertaken to study the metabolic response of C6 glioma cells to physiologically relevant doses of delta9-tetrahydrocannabinol (THC), the major active component of marijuana. At those concentrations (i.e. nanomolar range), THC produced a dose-dependent increase in the rates of glucose oxidation to CO2 and glucose incorporation into phospholipids and glycogen. The THC-induced stimulation of glucose utilization was (i) dose-dependent up to 100 nM THC, (ii) mimicked by the synthetic cannabinoid HU-210, and (iii) prevented by pertussis toxin and the CB1 receptor antagonist SR141716A. In contrast to THC, forskolin markedly depressed CO2 production, phospholipid synthesis and glycogen synthesis from glucose. The forskolin-induced inhibition of glucose utilization was (i) mimicked by dibutyryl-cAMP, and (ii) prevented by THC, HU-210 and H-7, an inhibitor of the cAMP-dependent protein kinase. Likewise, THC was able to antagonize in part the forskolin-induced elevation of intracellular cAMP concentration, and this antagonistic effect was prevented by SR141716A. However, THC per se did not affect basal cAMP concentration. Results thus indicate that physiologically relevant doses of THC stimulate glucose metabolism in C6 glioma cells through a cannabinoid receptor-mediated process. Although cannabinoid receptors may be coupled to inhibition of adenylyl cyclase in C6 glioma cells, this does not seem to be the mechanism involved in the THC-induced stimulation of glucose metabolism.

Topics: Dronabinol; Glioma; Glucose; Glycogen; Oxidation-Reduction; Phospholipids; Stimulation, Chemical; Tumor Cells, Cultured

A mathematical model of mammalian cell intermediary metabolism is presented. It describes the distribution of the carbon-13 isotope (13C) at the different carbon positions of metabolites in cells fed with 13C-enriched substrates. The model allows the determination of fluxes through different metabolic pathways from 13C- and 1H-NMR spectroscopy and mass spectrometry data. The considered metabolic network includes glycolysis, gluconeogenesis, the citric acid cycle and a number of reactions corresponding to protein or fatty acid metabolism. The model was used for calculating metabolic fluxes in a rat tumor cell line, the C6 glioma, incubated with [1-13C]glucose. After evolution to metabolic and isotopic steady states, the intracellular metabolites were extracted with perchloric acid. The specific enrichments of glutamate, aspartate and alanine carbons were determined from 13C-, 1H-NMR spectroscopy, or mass spectrometry data. Taking into account the rate of glucose consumption and of lactate formation, determined from the evolution of glucose and lactate contents in the cell medium, and knowing the activity of the hexose monophosphate shunt, it was possible to estimate the absolute values of all the considered fluxes. From the analysis the following results were obtained. (a) Glucose accounts for about 78% of the pyruvate and 57% of the CoASAc. (b) A metabolic channelling occurs at the citric acid cycle level; it favours the conversion of carbons 2, 3, 4, and 5 of 2-oxoglutarate into carbons 1, 2, 3, and 4 of oxaloacetate, respectively. The percentage of channelled metabolites amounts to 39%. (c) The pyruvate carboxylase activity and the efflux from the citric acid cycle are estimated to be very low, suggesting a lack of glutamine production in C6 cells. The results emphasize different metabolic characteristics of C6 cells when compared to astrocytes, their normal counterpart.

Topics: Alanine; Aspartic Acid; Carbon Isotopes; Citric Acid Cycle; Glioma; Gluconeogenesis; Glucose; Glutamates; Glutamic Acid; Glycogen; Glycolysis; Kinetics; Magnetic Resonance Spectroscopy; Malate Dehydrogenase; Mathematics; Models, Biological; Pentose Phosphate Pathway; Perchlorates; Pyruvates; Pyruvic Acid; Tumor Cells, Cultured

Biopsies from 15 human gliomas, five meningiomas, four Schwannomas, one medulloblastoma, and four normal brain areas were analyzed for 12 enzymes of energy metabolism and 12 related metabolites and cofactors. Samples, 0.01-0.25 microgram dry weight, were dissected from freeze-dried microtome sections to permit all the assays on a given specimen to be made, as far as possible, on nonnecrotic pure tumor tissue from the same region. Great diversity was found with regard to both enzyme activities and metabolite levels among individual tumors, but the following generalities can be made. Activities of hexokinase, phosphorylase, phosphofructokinase, glycerophosphate dehydrogenase, citrate synthase, and malate dehydrogenase levels were usually lower than in brain; glycogen synthase and glucose-6-phosphate dehydrogenase were usually higher; and the averages for pyruvate kinase, lactate dehydrogenase, 6-phosphogluconate dehydrogenase, and beta-hydroxyacyl coenzyme A dehydrogenase were not greatly different from brain. Levels of eight of the 12 enzymes were distinctly lower among the Schwannomas than in the other two groups. Average levels of glucose-6-phosphate, lactate, pyruvate, and uridine diphosphoglucose were more than twice those of brain; 6-phosphogluconate and citrate were about 70% higher than in brain; glucose, glycogen, glycerol-1-phosphate, and malate averages ranged from 104% to 127% of brain; and fructose-1,6-bisphosphate and glucose-1,6-bisphosphate levels were on the average 50% and 70% those of brain, respectively.

Topics: Adolescent; Adult; Aged; Brain; Brain Neoplasms; Child; Child, Preschool; Energy Metabolism; Female; Glioma; Glycogen; Glycolysis; Humans; Male; Medulloblastoma; Meningioma; Middle Aged; Mitochondria; Neurilemmoma; Oxidative Phosphorylation

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Adolescent; Adult; Aged; Brain Neoplasms; Child; Creatine Kinase; Energy Metabolism; Female; Glioma; Glycogen; Humans; Lipids; Male; Meningioma; Middle Aged; Neurilemmoma; Phosphates; Phosphocreatine; Uridine Triphosphate

Topics: Animals; Bromodeoxyuridine; Cell Differentiation; Cell Line; Clone Cells; Dactinomycin; Desmosomes; Glioma; Glycogen; In Vitro Techniques; Methotrexate; Microscopy, Electron; Microscopy, Phase-Contrast; Rats; Stimulation, Chemical

Topics: Adenine Nucleotides; Adenosine Triphosphate; Brain; Brain Neoplasms; Fluorometry; Frontal Lobe; Glioma; Glucose; Glycogen; Glycolysis; Hexoses; Humans; In Vitro Techniques; Ischemia; Lactates; Phosphocreatine; Spectrophotometry; Tissue Extracts

Topics: Adenosine Triphosphate; Animals; Brain; Brain Chemistry; Fluorometry; Glioma; Glucose; Glycogen; Ischemic Attack, Transient; Lactates; Methylcholanthrene; Mice; Neoplasms, Experimental; Phosphocreatine

Topics: Animals; Brain Chemistry; Ethanol; Fluorescence; Glioma; Glucosephosphate Dehydrogenase; Glycogen; Hydrogen-Ion Concentration; Mice; NADP; Neoplasms, Experimental; Nucleic Acids; Phospholipids; Phosphorus; Phosphotransferases; Spectrum Analysis

Topics: Cell Division; Cytoplasm; Eye Neoplasms; Glioma; Glycogen; Humans; Melanoma; Necrosis

Topics: Eye Neoplasms; Glioma; Glycogen; Humans; Melanoma

Topics: Astrocytoma; Brain Neoplasms; Carbohydrate Metabolism; Cerebellar Neoplasms; Ependymoma; Glioma; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Lipid Metabolism; Lipids; Medulloblastoma; Meningeal Neoplasms; Meningioma