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Cited by 177Biochemical Acid Research StudiesNeuroscience and Neuropharmacology ResearchMitochondrial Function and Pathology

Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of cultured rat brain astrocytes and neurons

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Halim, Nader D., Mcfate, Thomas, Mohyeldin, Ahmed, Okagaki, Peter, Korotchkina, Lioubov G., Patel, Mulchand S., Jeoung, Nam Ho, Harris, Robert A. +2 more·2010·Glia
DOI 10.1002/glia.20996PMC PMC2915787
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Abstract

Glucose metabolism in nervous tissue has been proposed to occur in a compartmentalized manner with astrocytes contributing largely to glycolysis and neurons being the primary site of glucose oxidation. However, mammalian astrocytes and neurons both contain mitochondria, and it remains unclear why in culture neurons oxidize glucose, lactate, and pyruvate to a much larger extent than astrocytes. The objective of this study was to determine whether pyruvate metabolism is differentially regulated in cultured neurons versus astrocytes. Expression of all components of the pyruvate dehydrogenase complex (PDC), the rate‐limiting step for pyruvate entry into the Krebs cycle, was determined in cultured astrocytes and neurons. In addition, regulation of PDC enzymatic activity in the two cell types via protein phosphorylation was examined. We show that all components of the PDC are expressed in both cell types in culture, but that PDC activity is kept strongly inhibited in astrocytes through phosphorylation of the pyruvate dehydrogenase alpha subunit (PDHα). In contrast, neuronal PDC operates close to maximal levels with much lower levels of phosphorlyated PDHα. Dephosphorylation of astrocytic PDHα restores PDC activity and lowers lactate production. Our findings suggest that the glucose metabolism of astrocytes and neurons may be far more flexible than previously believed. © 2010 Wiley‐Liss, Inc.

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  • Phosphorylation-mediated inactivation of Pdh in astrocytes prevents glycolytic pyruvate from entering oxidative phosphorylation.

    “Phosphorylation-mediated inactivation of Pdh in astrocytes (Itoh et al., 2003;Halim et al., 2010) prevents glycolytic pyruvate from entering oxidative phosphorylation.”

    From An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex (2014) · cites this paper as Halim et al., 2010

    The Discussion says PDHα phosphorylation may block pyruvate from entering the Krebs cycle, and the Results show that reducing phosphorylation lowers lactate production in cultured astrocytes. The claim states this as an unqualified prevention in astrocytes generally, whereas the paper presents it as a possible mechanism based on cultured cells and also discusses astroglial pyruvate oxidation in vivo. (LLM, conf=0.87)

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Authors
Halim, N. D., Mcfate, T., Mohyeldin, A., Okagaki, P., Korotchkina, L. G., Patel, M. S., Jeoung, N. H., Harris, R. A., Schell, M. J., & Verma, A.
Affiliations
  • Uniformed Services University of the Health Sciences (US)
  • University at Buffalo, State University of New York (US)
  • Indiana University Indianapolis (US)
Corresponding author
Schell, Michael J.
ORCID
Venue
Glia
Publisher
Wiley
Published
2010-04-09
Volume
58
Issue
10
Pages
1168-1176
ISSN
  • 0894-1491 (ISSN-L)
  • 1098-1136
DOI
10.1002/glia.20996
PMC
PMC2915787
OpenAlex
W2113402112
Cited by
177
References
3
Citations by year
2026: 10 · 2025: 8 · 2024: 14 · 2023: 13 · 2022: 11 · 2021: 11 · 2020: 14 · 2019: 9 · 2018: 16 · 2017: 17 · 2016: 8 · 2015: 10 · 2014: 10 · 2013: 8 · 2012: 11
FWCI
4.04
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Glia (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
  • NIH (NS37814, CA113506, DK42885, DK47844)
  • Department of Defense (DOD) (MDA905-03-2-0001)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
pyruvate dehydrogenase complex, protein phosphorylation, astrocytes, neurons, brain glucose metabolism, pyruvate metabolism, lactic acid production, dephosphorylation, TCA cycle
MeSH terms
Animals, Astrocytes, Brain, Cells, Cultured, Immunohistochemistry, L-Lactate Dehydrogenase, Neurons, Phosphorylation, Pyruvate Dehydrogenase Complex, Immunoblotting, Electrophoresis, Gel, Two-Dimensional, Rats, Sprague-Dawley, Coculture Techniques, Lactic Acid, Rats

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