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.
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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 |
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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 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: | https://discovery.ucl.ac.uk/id/eprint/1538225 |
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