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Proton Fall or Bicarbonate Rise: Glycolytic Rate In Mouse Astrocytes Is Paved By Intracellular Alkalinization

Theparambil, SM; Weber, T; Schmälzle, J; Ruminot, I; Deitmer, JW; (2016) Proton Fall or Bicarbonate Rise: Glycolytic Rate In Mouse Astrocytes Is Paved By Intracellular Alkalinization. Journal of Biological Chemistry , 291 (36) pp. 19108-19117. 10.1074/jbc.M116.730143. Green open access

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Abstract

Glycolysis is the primary step for major energy production in the cell. There is strong evidence suggesting that glucose consumption and rate of glycolysis are highly modulated by cytosolic pH/[H(+)], but those can also be stimulated by an increase in the intracellular [HCO3 (-)]. Because proton and bicarbonate shift concomitantly, it remained unclear whether enhanced glucose consumption and glycolytic rate were mediated by the changes in intracellular [H(+)] or [HCO3 (-)]. We have asked whether glucose metabolism is enhanced by either a fall in intracellular [H(+)] or a rise in intracellular [HCO3 (-)], or by both, in mammalian astrocytes. We have recorded intracellular glucose in mouse astrocytes using a FRET-based nanosensor, while imposing different intracellular [H(+)] and [CO2]/[HCO3 (-)]. Glucose consumption and glycolytic rate were augmented by a fall in intracellular [H(+)], irrespective of a concomitant rise or fall in intracellular [HCO3 (-)]. Transport of HCO3 (-) into and out of astrocytes by the electrogenic sodium bicarbonate cotransporter (NBCe1) played a crucial role in causing changes in intracellular pH and [HCO3 (-)], but was not obligatory for the pH-dependent changes in glucose metabolism. Our results clearly show that it is the cytosolic pH that modulates glucose metabolism in cortical astrocytes, and possibly also in other cell types.

Type: Article
Title: Proton Fall or Bicarbonate Rise: Glycolytic Rate In Mouse Astrocytes Is Paved By Intracellular Alkalinization
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1074/jbc.M116.730143
Publisher version: http://dx.doi.org/10.1074/jbc.M116.730143
Language: English
Additional information: Copyright © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Keywords: FRET nanosensor, FRET nanosensors, astrocyte, astrocytes, bicarbonate, brain metabolism, glucose, metabolism, pH
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1538225
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