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Cited by 64Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismCancer, Hypoxia, and Metabolism

α‐cyano‐4‐hydroxycinnamate decreases both glucose and lactate metabolism in neurons and astrocytes: Implications for lactate as an energy substrate for neurons

McKenna, Mary C., Hopkins, Irene B., Carey, Adrienne·2001·Journal of Neuroscience Research
DOI 10.1002/jnr.10084
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Abstract

The rates of uptake and oxidation of [U-(14)C]lactate and [U-(14)C]glucose were determined in primary cultures of astrocytes and neurons from rat brain, in the presence and absence of the monocarboxylic acid transport inhibitor alpha-cyano-4-hydroxycinnamate (4-CIN). The rates of uptake for 1 mM lactate and glucose were 7.45 +/- 1.35 and 8.80 +/- 1.0 nmol/30 sec/mg protein in astrocytes and 2.36 +/- 0.19 and 1.93 +/- 0.16 nmol/30 sec/mg protein in neuron cultures, respectively. Lactate transport into both astrocytes and neurons was significantly decreased by 0.25-1.0 mM 4-CIN; however, glucose uptake was not affected. The rates of (14)CO(2) formation from 1 mM lactate and glucose were 12.49 +/- 0.77 and 3.42 +/- 0.67 nmol/hr/mg protein in astrocytes and 29.32 +/- 2.81 and 10.04 +/- 1.79 nmol/hr/mg protein in neurons, respectively. Incubation with 0.25 mM 4-CIN decreased the oxidation of lactate and glucose to 57.1% and 54.1% of control values in astrocytes and to 13.2% and 41.6% of the control rates in neurons, respectively. Preincubation with 4-CIN further decreased the oxidation of both glucose and lactate. Studies with glucose specifically labeled in the one and six positions demonstrated that 4-CIN decreased mitochondrial glucose oxidation but did not impair the metabolism of glucose via the pentose phosphate pathway in the cytosol. The lack of effect of 4-CIN on glutamate oxidation demonstrated that overall mitochondrial metabolism was not impaired. These findings suggest that the impaired neuronal function and tissue damage in the presence of 4-CIN observed in other studies may be due in part to decreased uptake of lactate; however, the effects of 4-CIN on mitochondrial transport would significantly decrease the oxidative metabolism of pyruvate derived from both glucose and lactate.

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  • The conclusion that lactate shuttling occurs under limited conditions is weak because MCT blockers that would also block mitochondrial pyruvate uptake were used.

    “this study argued for lactate shuttling under limited conditions, but this conclusion is weak because MCT blockers that would also block mitochondrial pyruvate uptake were used (Halestrap and Denton, 1975; McKenna et al., 2001).”

    From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as McKenna et al., 2001

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Authors
McKenna, M. C., Hopkins, I. B., & Carey, A.
Affiliations
University of Maryland, Baltimore (US)
Corresponding author
McKenna, Mary C.
ORCID
Venue
Journal of Neuroscience Research
Publisher
Wiley
Published
2001-11-30
Volume
66
Issue
5
Pages
747-754
ISSN
  • 0360-4012 (ISSN-L)
  • 1097-4547
DOI
10.1002/jnr.10084
OpenAlex
W1994274791
Cited by
64
References
63
Citations by year
2026: 1 · 2025: 2 · 2024: 4 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 3
FWCI
1.84
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neuroscience Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD16596, P01HD016596)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
HCCA, lactate transport, glucose transport, lactate oxidation, glucose oxidation, astrocytes, neurons, monocarboxylate transport, mitochondrial transport, neuronal energy metabolism, pyruvate oxidation, pentose phosphate pathway, glutamate oxidation
MeSH terms
Animals, Astrocytes, Brain, Carbon Dioxide, Carbon Radioisotopes, Cells, Cultured, Coumaric Acids, Dose-Response Relationship, Drug, Female, Fetus, Glucose, Monosaccharide Transport Proteins, Neurons, Oxidative Phosphorylation, Pregnancy, Down-Regulation, Pyruvic Acid, Lactic Acid, Rats

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