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Cited by 22Mitochondrial Function and PathologyNeuroscience and Neuropharmacology ResearchAmino Acid Enzymes and Metabolism

Consumption and Metabolism of Extracellular Pyruvate by Cultured Rat Brain Astrocytes

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Denker, Nadine, Harders, Antonia R., Arend, Christian, Dringen, Ralf·2023·Neurochemical Research
DOI 10.1007/s11064-022-03831-6PMC PMC10066139
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Abstract

Brain astrocytes are considered as glycolytic cell type, but these cells also produce ATP via mitochondrial oxidative phosphorylation. Exposure of cultured primary astrocytes in a glucose-free medium to extracellular substrates that are known to be metabolised by mitochondrial pathways, including pyruvate, lactate, beta-hydroxybutyrate, alanine and acetate, revealed that among the substrates investigated extracellular pyruvate was most efficiently consumed by astrocytes. Extracellular pyruvate was consumed by the cells almost proportional to time over hours in a concentration-dependent manner with apparent Michaelis–Menten kinetics [K m = 0.6 ± 0.1 mM, V max = 5.1 ± 0.8 nmol/(min × mg protein)]. The astrocytic consumption of pyruvate was strongly impaired in the presence of the monocarboxylate transporter 1 (MCT1) inhibitor AR-C155858 or by application of a 10-times excess of the MCT1 substrates lactate or beta-hydroxybutyrate. Pyruvate consumption by viable astrocytes was inhibited in the presence of UK5099, an inhibitor of the mitochondrial pyruvate carrier, or after application of the respiratory chain inhibitor antimycin A. In contrast, the mitochondrial uncoupler BAM15 strongly accelerated cellular pyruvate consumption. Lactate and alanine accounted after 3 h of incubation with pyruvate for around 60% and 10%, respectively, of the pyruvate consumed by the cells. These results demonstrate that consumption of extracellular pyruvate by astrocytes involves uptake via MCT1 and that the velocity of pyruvate consumption is strongly modified by substances that affect the entry of pyruvate into mitochondria or the activity of mitochondrial respiration.

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Authors
Denker, N., Harders, A. R., Arend, C., & Dringen, R.
Affiliations
University of Bremen (DE)
Corresponding author
Dringen, Ralf
ORCID
Venue
Neurochemical Research
Publisher
Springer Science and Business Media LLC
Published
2022-12-10
Volume
48
Issue
5
Pages
1438-1454
ISSN
  • 0364-3190 (ISSN-L)
  • 1573-6903
DOI
10.1007/s11064-022-03831-6
PMC
PMC10066139
OpenAlex
W4311023715
Cited by
22
References
1
Citations by year
2026: 3 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 1
FWCI
1.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurochemical Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Universität Bremen
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
astrocytes, pyruvate uptake, MCT1, mitochondrial pyruvate carrier, mitochondrial respiration, oxidative phosphorylation, lactate, beta-hydroxybutyrate, alanine, acetate, Michaelis-Menten kinetics, UK5099, antimycin A, BAM15, brain energy metabolism
MeSH terms
Alanine, Animals, Astrocytes, Brain, Carrier Proteins, Lactates, Pyruvic Acid, 3-Hydroxybutyric Acid, Rats

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