Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes. / Pajęcka, Kamilla; Nissen, Jakob D; Stridh, Malin H; Skytt, Dorte M; Schousboe, Arne; Waagepetersen, Helle S.

In: Journal of Neuroscience Research, Vol. 93, No. 7, 07.2015, p. 1093-100.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Pajęcka, K, Nissen, JD, Stridh, MH, Skytt, DM, Schousboe, A & Waagepetersen, HS 2015, 'Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes', Journal of Neuroscience Research, vol. 93, no. 7, pp. 1093-100. https://doi.org/10.1002/jnr.23568

APA

Pajęcka, K., Nissen, J. D., Stridh, M. H., Skytt, D. M., Schousboe, A., & Waagepetersen, H. S. (2015). Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes. Journal of Neuroscience Research, 93(7), 1093-100. https://doi.org/10.1002/jnr.23568

Vancouver

Pajęcka K, Nissen JD, Stridh MH, Skytt DM, Schousboe A, Waagepetersen HS. Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes. Journal of Neuroscience Research. 2015 Jul;93(7):1093-100. https://doi.org/10.1002/jnr.23568

Author

Pajęcka, Kamilla ; Nissen, Jakob D ; Stridh, Malin H ; Skytt, Dorte M ; Schousboe, Arne ; Waagepetersen, Helle S. / Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes. In: Journal of Neuroscience Research. 2015 ; Vol. 93, No. 7. pp. 1093-100.

Bibtex

@article{fb75805ec33d4555b0d84dfeadb503c0,
title = "Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes",
abstract = "Cultured astrocytes treated with siRNA to knock down glutamate dehydrogenase (GDH) were used to investigate whether this enzyme is important for the utilization of glutamate as an energy substrate. By incubation of these cells in media containing different concentrations of glutamate (range 100-500 µM) in the presence or in the absence of glucose, the metabolism of these substrates was studied by using tritiated glutamate or 2-deoxyglucose as tracers. In addition, the cellular contents of glutamate and ATP were determined. The astrocytes were able to maintain physiological levels of ATP regardless of the expression level of GDH and the incubation condition, indicating a high degree of flexibility with regard to regulatory mechanisms involved in maintaining an adequate energy level in the cells. Glutamate uptake was found to be increased in these cells when exposed to increasing levels of extracellular glutamate independently of the GDH expression level. Moreover, increased intracellular glutamate content was observed in the GDH-deficient cells after a 2-hr incubation in the presence of 100 µM glutamate. It is significant that GDH-deficient cells exhibited an increased utilization of glucose in the presence of 250 and 500 µM glutamate, monitored as an increase in the accumulation of tritiated 2-deoxyglucose-6-phosphate. These findings underscore the importance of the expression level of GDH for the ability to utilize glutamate as an energy source fueling its own energy-requiring uptake.",
keywords = "Adenosine Triphosphate, Analysis of Variance, Animals, Animals, Newborn, Astrocytes, Cells, Cultured, Cerebral Cortex, Dose-Response Relationship, Drug, Extracellular Fluid, Glucose, Glucose-6-Phosphate, Glutamate Dehydrogenase, Glutamic Acid, Mice, Mice, Inbred Strains, RNA, Small Interfering",
author = "Kamilla Pajęcka and Nissen, {Jakob D} and Stridh, {Malin H} and Skytt, {Dorte M} and Arne Schousboe and Waagepetersen, {Helle S}",
note = "{\circledC} 2015 Wiley Periodicals, Inc.",
year = "2015",
month = "7",
doi = "10.1002/jnr.23568",
language = "English",
volume = "93",
pages = "1093--100",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "JohnWiley & Sons, Inc.",
number = "7",

}

RIS

TY - JOUR

T1 - Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes

AU - Pajęcka, Kamilla

AU - Nissen, Jakob D

AU - Stridh, Malin H

AU - Skytt, Dorte M

AU - Schousboe, Arne

AU - Waagepetersen, Helle S

N1 - © 2015 Wiley Periodicals, Inc.

PY - 2015/7

Y1 - 2015/7

N2 - Cultured astrocytes treated with siRNA to knock down glutamate dehydrogenase (GDH) were used to investigate whether this enzyme is important for the utilization of glutamate as an energy substrate. By incubation of these cells in media containing different concentrations of glutamate (range 100-500 µM) in the presence or in the absence of glucose, the metabolism of these substrates was studied by using tritiated glutamate or 2-deoxyglucose as tracers. In addition, the cellular contents of glutamate and ATP were determined. The astrocytes were able to maintain physiological levels of ATP regardless of the expression level of GDH and the incubation condition, indicating a high degree of flexibility with regard to regulatory mechanisms involved in maintaining an adequate energy level in the cells. Glutamate uptake was found to be increased in these cells when exposed to increasing levels of extracellular glutamate independently of the GDH expression level. Moreover, increased intracellular glutamate content was observed in the GDH-deficient cells after a 2-hr incubation in the presence of 100 µM glutamate. It is significant that GDH-deficient cells exhibited an increased utilization of glucose in the presence of 250 and 500 µM glutamate, monitored as an increase in the accumulation of tritiated 2-deoxyglucose-6-phosphate. These findings underscore the importance of the expression level of GDH for the ability to utilize glutamate as an energy source fueling its own energy-requiring uptake.

AB - Cultured astrocytes treated with siRNA to knock down glutamate dehydrogenase (GDH) were used to investigate whether this enzyme is important for the utilization of glutamate as an energy substrate. By incubation of these cells in media containing different concentrations of glutamate (range 100-500 µM) in the presence or in the absence of glucose, the metabolism of these substrates was studied by using tritiated glutamate or 2-deoxyglucose as tracers. In addition, the cellular contents of glutamate and ATP were determined. The astrocytes were able to maintain physiological levels of ATP regardless of the expression level of GDH and the incubation condition, indicating a high degree of flexibility with regard to regulatory mechanisms involved in maintaining an adequate energy level in the cells. Glutamate uptake was found to be increased in these cells when exposed to increasing levels of extracellular glutamate independently of the GDH expression level. Moreover, increased intracellular glutamate content was observed in the GDH-deficient cells after a 2-hr incubation in the presence of 100 µM glutamate. It is significant that GDH-deficient cells exhibited an increased utilization of glucose in the presence of 250 and 500 µM glutamate, monitored as an increase in the accumulation of tritiated 2-deoxyglucose-6-phosphate. These findings underscore the importance of the expression level of GDH for the ability to utilize glutamate as an energy source fueling its own energy-requiring uptake.

KW - Adenosine Triphosphate

KW - Analysis of Variance

KW - Animals

KW - Animals, Newborn

KW - Astrocytes

KW - Cells, Cultured

KW - Cerebral Cortex

KW - Dose-Response Relationship, Drug

KW - Extracellular Fluid

KW - Glucose

KW - Glucose-6-Phosphate

KW - Glutamate Dehydrogenase

KW - Glutamic Acid

KW - Mice

KW - Mice, Inbred Strains

KW - RNA, Small Interfering

U2 - 10.1002/jnr.23568

DO - 10.1002/jnr.23568

M3 - Journal article

C2 - 25656783

VL - 93

SP - 1093

EP - 1100

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 7

ER -

ID: 156853768