Metabolic alterations induced by ischemia in primary cultures of astrocytes: Merging 13C NMR spectroscopy and metabolic flux analysis

Journal of Neurochemistry

Volumn 113, Issue 3, 2010, Pages 735-748

  Amaral, Ana I ^a   Teixeira, Ana P ^a   Martens, Sanja ^a   Bernal, Vicente ^a   Sousa, Marcos F Q ^a   Alves, Paula M ^a  

^a INSTITUTO DE TECNOLOGIA QUÍMICA E BIOLÓGICA   (Portugal)

Author keywords

Astrocytes; Bioreactor; Energy metabolism; Ischemia; Metabolic flux analysis; Oxygen monitoring

Indexed keywords

ADENOSINE TRIPHOSPHATE; BRANCHED CHAIN AMINO ACID; CARBON 13; PENTOSE PHOSPHATE; TRICARBOXYLIC ACID;

AMINO ACID METABOLISM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ASTROCYTE; BRAIN ISCHEMIA; BRAIN METABOLISM; CARBON NUCLEAR MAGNETIC RESONANCE; CATABOLISM; CELL FUNCTION; CELL METABOLISM; CELL SURVIVAL; CONTROLLED STUDY; ENERGY METABOLISM; GLUCOSE METABOLISM; GLUCOSE UTILIZATION; METABOLITE; NERVE CELL NECROSIS; NONHUMAN; PRIORITY JOURNAL; RAT; UPREGULATION;

ADENOSINE TRIPHOSPHATE; AMINO ACIDS; AMINO ACIDS, BRANCHED-CHAIN; ANIMALS; ASTROCYTES; BIOREACTORS; BRAIN ISCHEMIA; CELL DEATH; CELL HYPOXIA; CELL SURVIVAL; CELLS, CULTURED; GLUCOSE; GLUTAMINE; GLYCOLYSIS; L-LACTATE DEHYDROGENASE; LACTIC ACID; MAGNETIC RESONANCE SPECTROSCOPY; NERVE TISSUE PROTEINS; OXIDATIVE PHOSPHORYLATION; PENTOSE PHOSPHATE PATHWAY; RATS; RATS, SPRAGUE-DAWLEY;

EID: 77950644610     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/j.1471-4159.2010.06636.x     Document Type: Article

References (67)

1. Alves P. M., Fonseca L. L., Peixoto C. C., Almeida A. C., Carrondo M. J. Santos H. (2000) NMR studies on energy metabolism of immobilized primary neurons and astrocytes during hypoxia, ischemia and hypoglycemia. NMR Biomed. 13, 438 448.
2. Bak L. K., Walls A. B., Schousboe A., Ring A., Sonnewald U. Waagepetersen H. S. (2009) Neuronal glucose but not lactate utilization is positively correlated with NMDA-induced neurotransmission and fluctuations in cytosolic Ca2+ levels. J. Neurochem. 109 (Suppl 1) 87 93.
3. Ben-Yoseph O., Boxer P. A. Ross B. D. (1994) Oxidative stress in the central nervous system: monitoring the metabolic response using the pentose phosphate pathway. Dev. Neurosci. 16, 328 336.
4. Ben-Yoseph O., Camp D. M., Robinson T. E. Ross B. D. (1995) Dynamic measurements of cerebral pentose phosphate pathway activity in vivo using [1,6-13C2,6,6-2H2]glucose and microdialysis. J. Neurochem. 64, 1336 1342.
5. Bergeron M., Yu A. Y., Solway K. E., Semenza G. L. Sharp F. R. (1999) Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain. Eur. J. Neurosci. 11, 4159 4170.
6. Berthet C., Lei H., Thevenet J., Gruetter R., Magistretti P. J. Hirt L. (2009) Neuroprotective role of lactate after cerebral ischemia. J. Cereb. Blood Flow Metab. 29, 1780 1789.
7. Bluml S., Moreno-Torres A., Shic F., Nguy C. H. Ross B. D. (2002) Tricarboxylic acid cycle of glia in the in vivo human brain. NMR Biomed. 15, 1 5.
8. Bolanos J. P., Cidad P., Garcia-Nogales P., Delgado-Esteban M., Fernandez E. Almeida A. (2004) Regulation of glucose metabolism by nitrosative stress in neural cells. Mol. Aspects Med. 25, 61 73.
9. Brand A., Leibfritz D., Hamprecht B. Dringen R. (1998) Metabolism of cysteine in astroglial cells: synthesis of hypotaurine and taurine. J. Neurochem. 71, 827 832.
10. Brown A. M. Ransom B. R. (2007) Astrocyte glycogen and brain energy metabolism. Glia 55, 1263 1271.
11. Carinhas N., Bernal V., Yokomizo A. Y., Carrondo M. J., Oliveira R. Alves P. M. (2009) Baculovirus production for gene therapy: the role of cell density, multiplicity of infection and medium exchange. Appl. Microbiol. Biotechnol. 81, 1041 1049.
12. Contreras L. Satrustegui J. (2009) Calcium signaling in brain mitochondria: interplay of malate aspartate NADH shuttle and calcium uniporter/mitochondrial dehydrogenase pathways. J. Biol. Chem. 284, 7091 7099.
13. Cruz N. F., Ball K. K. Dienel G. A. (2007) Functional imaging of focal brain activation in conscious rats: impact of [(14)C]glucose metabolite spreading and release. J. Neurosci. Res. 85, 3254 3266.
14. Danbolt N. C. (2001) Glutamate uptake. Prog. Neurobiol. 65, 1 105.
15. Dankberg F. Persidsky M. D. (1976) A test of granulocyte membrane integrity and phagocytic function. Cryobiology 13, 430 432.
16. Dienel G. A. Cruz N. F. (2009) Exchange-mediated dilution of brain lactate specific activity: implications for the origin of glutamate dilution and the contributions of glutamine dilution and other pathways. J. Neurochem. 109 (Suppl 1 30 37.
17. Dienel G. A. Hertz L. (2001) Glucose and lactate metabolism during brain activation. J. Neurosci. Res. 66, 824 838.
18. Dienel G. A. Hertz L. (2005) Astrocytic contributions to bioenergetics of cerebral ischemia. Glia 50, 362 388.
19. Dienel G. A., Ball K. K. Cruz N. F. (2007) A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover. J. Neurochem. 102, 466 478.
20. Dirnagl U., Iadecola C. Moskowitz M. A. (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 22, 391 397.
21. Dringen R. (2000) Glutathione metabolism and oxidative stress in neurodegeneration. Eur. J. Biochem. 267, 4903.
22. Dringen R., Gebhardt R. Hamprecht B. (1993) Glycogen in astrocytes: possible function as lactate supply for neighboring cells. Brain Res. 623, 208 214.
23. Frykholm P., Hillered L., Langstrom B., Persson L., Valtysson J. Enblad P. (2005) Relationship between cerebral blood flow and oxygen metabolism, and extracellular glucose and lactate concentrations during middle cerebral artery occlusion and reperfusion: a microdialysis and positron emission tomography study in nonhuman primates. J. Neurosurg. 102, 1076 1084.
24. Garcia-Nogales P., Almeida A., Fernandez E., Medina J. M. Bolanos J. P. (1999) Induction of glucose-6-phosphate dehydrogenase by lipopolysaccharide contributes to preventing nitric oxide-mediated glutathione depletion in cultured rat astrocytes. J. Neurochem. 72, 1750 1758.
25. Haberg A., Qu H., Saether O., Unsgard G., Haraldseth O. Sonnewald U. (2001) Differences in neurotransmitter synthesis and intermediary metabolism between glutamatergic and GABAergic neurons during 4 hours of middle cerebral artery occlusion in the rat: the role of astrocytes in neuronal survival. J. Cereb. Blood Flow Metab. 21, 1451 1463.
26. Haberg A., Qu H. Sonnewald U. (2006) Glutamate and GABA metabolism in transient and permanent middle cerebral artery occlusion in rat: importance of astrocytes for neuronal survival. Neurochem. Int. 48 (6-7 531 540.
27. Hertz L. (2008) Bioenergetics of cerebral ischemia: a cellular perspective. Neuropharmacology 55, 289 309.
28. Hertz L., Peng L. Dienel G. A. (2007) Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J. Cereb. Blood Flow Metab. 27, 219 249.
29. Hyder F., Patel A. B., Gjedde A., Rothman D. L., Behar K. L. Shulman R. G. (2006) Neuronal-glial glucose oxidation and glutamatergic-GABAergic function. J. Cereb. Blood Flow Metab. 26, 865 877.
30. Johansen M. L., Bak L. K., Schousboe A., Iversen P., Sorensen M., Keiding S., Vilstrup H., Gjedde A., Ott P. Waagepetersen H. S. (2007) The metabolic role of isoleucine in detoxification of ammonia in cultured mouse neurons and astrocytes. Neurochem. Int. 50, 1042 1051.
31. Juurlink B. H. (1997) Response of glial cells to ischemia: roles of reactive oxygen species and glutathione. Neurosci. Biobehav. Rev. 21, 151 166.
32. Klamt S., Saez-Rodriguez J. Gilles E. D. (2007) Structural and functional analysis of cellular networks with CellNetAnalyzer. BMC Syst. Biol. 1, 2.
33. Kranich O., Hamprecht B. Dringen R. (1996) Different preferences in the utilization of amino acids for glutathione synthesis in cultured neurons and astroglial cells derived from rat brain. Neurosci. Lett. 219, 211 214.
34. Kussmaul L., Hamprecht B. Dringen R. (1999) The detoxification of cumene hydroperoxide by the glutathione system of cultured astroglial cells hinges on hexose availability for the regeneration of NADPH. J. Neurochem. 73, 1246 1253.
35. Lebon V., Petersen K. F., Cline G. W., Shen J., Mason G. F., Dufour S., Behar K. L., Shulman G. I. Rothman D. L. (2002) Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J. Neurosci. 22, 1523 1531.
36. Lee K., Berthiaume F., Stephanopoulos G. N. Yarmush M. L. (1999) Metabolic flux analysis: a powerful tool for monitoring tissue function. Tissue Eng. 5, 347 368.
37. Li A. L. Gao L. X. (1999) Protection of branched-chain amino acids against ischemic myocardial injury in rats. Biomed. Environ. Sci. 12, 62 65.
38. Lipton P. (1999) Ischemic cell death in brain neurons. Physiol. Rev. 79, 1431 1568.
39. Mangia S., Simpson I. A., Vannucci S. J. Carruthers A. (2009) The in vivo neuron-to-astrocyte lactate shuttle in human brain: evidence from modeling of measured lactate levels during visual stimulation. J. Neurochem. 109 (Suppl 1 55 62.
40. Murin R., Mohammadi G., Leibfritz D. Hamprecht B. (2009a) Glial metabolism of isoleucine. Neurochem. Res. 34, 194 204.
41. Murin R., Mohammadi G., Leibfritz D. Hamprecht B. (2009b) Glial metabolism of valine. Neurochem. Res. 34, 1195 1203.
42. Pascual J. M., Carceller F., Roda J. M. Cerdan S. (1998) Glutamate, glutamine, and GABA as substrates for the neuronal and glial compartments after focal cerebral ischemia in rats. Stroke 29, 1048 1056 discussion 1056-1057.
43. Pellerin L. Magistretti P. J. (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl Acad. Sci. USA 91, 10625 10629.
44. Pellerin L., Bouzier-Sore A. K., Aubert A., Serres S., Merle M., Costalat R. Magistretti P. J. (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55, 1251 1262.
45. Phillis J. W., Ren J. O'Regan M. H. (2001) Studies on the effects of lactate transport inhibition, pyruvate, glucose and glutamine on amino acid, lactate and glucose release from the ischemic rat cerebral cortex. J. Neurochem. 76, 247 257.
46. Racher A. J., Looby D. Griffiths J. B. (1990) Use of lactate dehydrogenase release to assess changes in culture viability. Cytotechnology 3, 301 307.
47. Richter-Landsberg C. Besser A. (1994) Effects of organotins on rat brain astrocytes in culture. J. Neurochem. 63, 2202 2209.
48. Riera J. J., Schousboe A., Waagepetersen H. S., Howarth C. Hyder F. (2008) The micro-architecture of the cerebral cortex: functional neuroimaging models and metabolism. Neuroimage 40, 1436 1459.
49. Rossi D. J., Brady J. D. Mohr C. (2007) Astrocyte metabolism and signaling during brain ischemia. Nat. Neurosci. 10, 1377 1386.
50. Sá Santos S., Fonseca L. L., Monteiro M. A., Carrondo M. J. Alves P. M. (2005) Culturing primary brain astrocytes under a fully controlled environment in a novel bioreactor. J. Neurosci. Res. 79, 26 32.
51. Schurr A. (2002) Lactate, glucose and energy metabolism in the ischemic brain (Review). Int. J. Mol. Med. 10, 131 136.
52. Shank R. P., Bennett G. S., Freytag S. O. Campbell G. L. (1985) Pyruvate carboxylase: an astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools. Brain Res. 329, 364 367.
53. Shank R. P., Leo G. C. Zielke H. R. (1993) Cerebral metabolic compartmentation as revealed by nuclear magnetic resonance analysis of D-[1-13C]glucose metabolism. J. Neurochem. 61, 315 323.
54. Shen J., Rothman D. L., Behar K. L. Xu S. (2009) Determination of the glutamate-glutamine cycling flux using two-compartment dynamic metabolic modeling is sensitive to astroglial dilution. J. Cereb. Blood Flow Metab. 29, 108 118.
55. Silver I. A., Deas J. Erecinska M. (1997) Ion homeostasis in brain cells: differences in intracellular ion responses to energy limitation between cultured neurons and glial cells. Neuroscience 78, 589 601.
56. Sochocka E., Juurlink B. H., Code W. E., Hertz V., Peng L. Hertz L. (1994) Cell death in primary cultures of mouse neurons and astrocytes during exposure to and 'recovery' from hypoxia, substrate deprivation and simulated ischemia. Brain Res. 638, 21 28.
57. Swanson R. A., Farrell K. Stein B. A. (1997) Astrocyte energetics, function, and death under conditions of incomplete ischemia: a mechanism of glial death in the penumbra. Glia 21, 142 153.
58. Szpetnar M., Pasternak K. Boguszewska A. (2004) Branched chain amino acids (BCAAs) in heart diseases (ischaemic heart disease and myocardial infarction). Ann. Univ. Mariae Curie Sklodowska [Med.] 59, 91 95.
59. Teixeira A. P., Santos S. S., Carinhas N., Oliveira R. Alves P. M. (2008) Combining metabolic flux analysis tools and (13)C NMR to estimate intracellular fluxes of cultured astrocytes. Neurochem. Int. 52, 478 486.
60. Tekkok S. B., Brown A. M., Westenbroek R., Pellerin L. Ransom B. R. (2005) Transfer of glycogen-derived lactate from astrocytes to axons via specific monocarboxylate transporters supports mouse optic nerve activity. J. Neurosci. Res. 81, 644 652.
61. Thoren A. E., Helps S. C., Nilsson M. Sims N. R. (2005) Astrocytic function assessed from 1-14C-acetate metabolism after temporary focal cerebral ischemia in rats. J. Cereb. Blood Flow Metab. 25, 440 450.
62. Varma A. Palsson B. O. (1994) Stoichiometric flux balance models quantitatively predict growth and metabolic by-product secretion in wild-type Escherichia coli W3110. Appl. Environ. Microbiol. 60, 3724 3731.
63. Walls A. B., Heimburger C. M., Bouman S. D., Schousboe A. Waagepetersen H. S. (2009) Robust glycogen shunt activity in astrocytes: Effects of glutamatergic and adrenergic agents. Neuroscience 158, 284 292.
64. Wang N. S. Stephanopoulos G. (1983) Application of macroscopic balances to the identification of gross measurement errors. Biotechnol. Bioeng. 25, 2177 2208. (Pubitemid 14526831)
65. Yager J. Y., Kala G., Hertz L. Juurlink B. H. (1994) Correlation between content of high-energy phosphates and hypoxic-ischemic damage in immature and mature astrocytes. Brain Res. Dev. Brain Res. 82, 62 68.
66. Yu A. C., Drejer J., Hertz L. Schousboe A. (1983) Pyruvate carboxylase activity in primary cultures of astrocytes and neurons. J. Neurochem. 41, 1484 1487. (Pubitemid 14227465)
67. Yudkoff M. (1997) Brain metabolism of branched-chain amino acids. Glia 21, 92 98.