Brain endothelial cells metabolize glutamate via glutamate dehydrogenase to replenish TCA-intermediates and produce ATP under hypoglycemic conditions

Research output: Contribution to journalJournal articlepeer-review

Standard

Brain endothelial cells metabolize glutamate via glutamate dehydrogenase to replenish TCA-intermediates and produce ATP under hypoglycemic conditions. / Hinca, Sven B; Salcedo, Claudia; Wagner, Antonie; Goldeman, Charlotte; Sadat, Edris; Aibar, Marco M D; Maechler, Pierre; Brodin, Birger; Aldana, Blanca I; Helms, Hans C C.

In: Journal of Neurochemistry, Vol. 157, No. 6, 2021, p. 1861-1875.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Hinca, SB, Salcedo, C, Wagner, A, Goldeman, C, Sadat, E, Aibar, MMD, Maechler, P, Brodin, B, Aldana, BI & Helms, HCC 2021, 'Brain endothelial cells metabolize glutamate via glutamate dehydrogenase to replenish TCA-intermediates and produce ATP under hypoglycemic conditions', Journal of Neurochemistry, vol. 157, no. 6, pp. 1861-1875. https://doi.org/10.1111/jnc.15207

APA

Hinca, S. B., Salcedo, C., Wagner, A., Goldeman, C., Sadat, E., Aibar, M. M. D., Maechler, P., Brodin, B., Aldana, B. I., & Helms, H. C. C. (2021). Brain endothelial cells metabolize glutamate via glutamate dehydrogenase to replenish TCA-intermediates and produce ATP under hypoglycemic conditions. Journal of Neurochemistry, 157(6), 1861-1875. https://doi.org/10.1111/jnc.15207

Vancouver

Hinca SB, Salcedo C, Wagner A, Goldeman C, Sadat E, Aibar MMD et al. Brain endothelial cells metabolize glutamate via glutamate dehydrogenase to replenish TCA-intermediates and produce ATP under hypoglycemic conditions. Journal of Neurochemistry. 2021;157(6):1861-1875. https://doi.org/10.1111/jnc.15207

Author

Hinca, Sven B ; Salcedo, Claudia ; Wagner, Antonie ; Goldeman, Charlotte ; Sadat, Edris ; Aibar, Marco M D ; Maechler, Pierre ; Brodin, Birger ; Aldana, Blanca I ; Helms, Hans C C. / Brain endothelial cells metabolize glutamate via glutamate dehydrogenase to replenish TCA-intermediates and produce ATP under hypoglycemic conditions. In: Journal of Neurochemistry. 2021 ; Vol. 157, No. 6. pp. 1861-1875.

Bibtex

@article{641664d3289d446e9a539f5c663e618e,
title = "Brain endothelial cells metabolize glutamate via glutamate dehydrogenase to replenish TCA-intermediates and produce ATP under hypoglycemic conditions",
abstract = "The endothelial cells of the blood-brain barrier participate in the regulation of glutamate concentrations in the brain interstitial fluid by taking up brain glutamate. However, endothelial glutamate metabolism has not been characterized, nor is its role in brain glutamate homeostasis and endothelial energy production known. The aim of this study was to investigate endothelial glutamate dehydrogenase (GDH) expression and glutamate metabolism and probe its functional significance. Primary brain endothelial cells were isolated from bovine and mouse brains, and human brain endothelial cells were derived from induced pluripotent stem cells. GDH expression on the protein level and GDH function were investigated in the model systems using western blotting, confocal microscopy, 13 C-glutamate metabolism and Seahorse assay. In the present study it was shown that GDH was expressed in murine and bovine brain capillaries and in cultured primary mouse and bovine brain endothelial cells as well as in human induced pluripotent stem cell-derived endothelial cells. The endothelial GDH expression was confirmed in brain capillaries from mice carrying a central nervous system specific GDH knockout. Endothelial cells from all tested species metabolized 13 C-glutamate to α-ketoglutarate, which subsequently entered the tricarboxylic acid (TCA)-cycle. Brain endothelial cells maintained mitochondrial oxygen consumption rates, when supplied with glutamate alone, whereas glutamate supplied in addition to glucose did not lead to additional oxygen consumption. In conclusion, brain endothelial cells directly take up and metabolize glutamate and utilize the resulting α-ketoglutarate in the TCA cycle to ultimately yield ATP if glucose is unavailable.",
author = "Hinca, {Sven B} and Claudia Salcedo and Antonie Wagner and Charlotte Goldeman and Edris Sadat and Aibar, {Marco M D} and Pierre Maechler and Birger Brodin and Aldana, {Blanca I} and Helms, {Hans C C}",
note = "This article is protected by copyright. All rights reserved.",
year = "2021",
doi = "10.1111/jnc.15207",
language = "English",
volume = "157",
pages = "1861--1875",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "6",

}

RIS

TY - JOUR

T1 - Brain endothelial cells metabolize glutamate via glutamate dehydrogenase to replenish TCA-intermediates and produce ATP under hypoglycemic conditions

AU - Hinca, Sven B

AU - Salcedo, Claudia

AU - Wagner, Antonie

AU - Goldeman, Charlotte

AU - Sadat, Edris

AU - Aibar, Marco M D

AU - Maechler, Pierre

AU - Brodin, Birger

AU - Aldana, Blanca I

AU - Helms, Hans C C

N1 - This article is protected by copyright. All rights reserved.

PY - 2021

Y1 - 2021

N2 - The endothelial cells of the blood-brain barrier participate in the regulation of glutamate concentrations in the brain interstitial fluid by taking up brain glutamate. However, endothelial glutamate metabolism has not been characterized, nor is its role in brain glutamate homeostasis and endothelial energy production known. The aim of this study was to investigate endothelial glutamate dehydrogenase (GDH) expression and glutamate metabolism and probe its functional significance. Primary brain endothelial cells were isolated from bovine and mouse brains, and human brain endothelial cells were derived from induced pluripotent stem cells. GDH expression on the protein level and GDH function were investigated in the model systems using western blotting, confocal microscopy, 13 C-glutamate metabolism and Seahorse assay. In the present study it was shown that GDH was expressed in murine and bovine brain capillaries and in cultured primary mouse and bovine brain endothelial cells as well as in human induced pluripotent stem cell-derived endothelial cells. The endothelial GDH expression was confirmed in brain capillaries from mice carrying a central nervous system specific GDH knockout. Endothelial cells from all tested species metabolized 13 C-glutamate to α-ketoglutarate, which subsequently entered the tricarboxylic acid (TCA)-cycle. Brain endothelial cells maintained mitochondrial oxygen consumption rates, when supplied with glutamate alone, whereas glutamate supplied in addition to glucose did not lead to additional oxygen consumption. In conclusion, brain endothelial cells directly take up and metabolize glutamate and utilize the resulting α-ketoglutarate in the TCA cycle to ultimately yield ATP if glucose is unavailable.

AB - The endothelial cells of the blood-brain barrier participate in the regulation of glutamate concentrations in the brain interstitial fluid by taking up brain glutamate. However, endothelial glutamate metabolism has not been characterized, nor is its role in brain glutamate homeostasis and endothelial energy production known. The aim of this study was to investigate endothelial glutamate dehydrogenase (GDH) expression and glutamate metabolism and probe its functional significance. Primary brain endothelial cells were isolated from bovine and mouse brains, and human brain endothelial cells were derived from induced pluripotent stem cells. GDH expression on the protein level and GDH function were investigated in the model systems using western blotting, confocal microscopy, 13 C-glutamate metabolism and Seahorse assay. In the present study it was shown that GDH was expressed in murine and bovine brain capillaries and in cultured primary mouse and bovine brain endothelial cells as well as in human induced pluripotent stem cell-derived endothelial cells. The endothelial GDH expression was confirmed in brain capillaries from mice carrying a central nervous system specific GDH knockout. Endothelial cells from all tested species metabolized 13 C-glutamate to α-ketoglutarate, which subsequently entered the tricarboxylic acid (TCA)-cycle. Brain endothelial cells maintained mitochondrial oxygen consumption rates, when supplied with glutamate alone, whereas glutamate supplied in addition to glucose did not lead to additional oxygen consumption. In conclusion, brain endothelial cells directly take up and metabolize glutamate and utilize the resulting α-ketoglutarate in the TCA cycle to ultimately yield ATP if glucose is unavailable.

U2 - 10.1111/jnc.15207

DO - 10.1111/jnc.15207

M3 - Journal article

C2 - 33025588

VL - 157

SP - 1861

EP - 1875

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 6

ER -

ID: 249773767