Protection by exogenous pyruvate through a mechanism related to monocarboxylate transporters against cell death induced by hydrogen peroxide in cultured rat cortical neurons
Abstract
In cortical neurons cultured for 3 or 9 days in vitro (DIV), exposure to hydrogen peroxide (H 2 O 2) led to a marked decrease in cell viability in a concentration‐dependent manner at a concentration range of 10 µ m to 1 m m irrespective of the duration between 6 and 24 h. However, H 2 O 2 was more potent in decreasing cellular viability in cortical neurons cultured for 9 DIV than in those for 3 DIV. Pyruvate was effective in preventing the neuronal cell death at 1 m m even when added 1–3 h after the addition of H 2 O 2. Semi‐quantitative RT–PCR and western blotting analyses revealed significantly higher expression of both mRNA and protein for a particular monocarboxylate transporter (MCT) in neurons cultured for 9 DIV than in those for 3 DIV. A specific inhibitor of MCT significantly attenuated the neuroprotection by pyruvate in neurons cultured for 9 DIV, without markedly affecting that in neurons cultured for 3 DIV. These results suggest that vulnerability to H 2 O 2 may at least in part involve expression of particular MCT isoforms responsible for the bi‐directional transport of pyruvate across cell surfaces in cultured rat cortical neurons.
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Additional pyruvate and lactic acid were included as energy-providing and neuroprotective substrates alongside standard oxidative substrates.
“We included additional pyruvate48, and lactic acid 49 as energy-providing and neuroprotective substrates in addition to the more canonical oxidative substrates (glucose, galactose and glutamine/Glutamax).”
From Efficient derivation of microglia-like cells from human pluripotent stem cells (2016) · cites this paper as [48]
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Efficient derivation of microglia-like cells from human pluripotent stem cells
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- Authors
- Nakamichi, N., Kambe, Y., Oikawa, H., Ogura, M., Takano, K., Tamaki, K., Inoue, M., Hinoi, E., & Yoneda, Y.
- Affiliations
- Kanazawa University (JP)
- Corresponding author
- Yoneda, Yukio
- ORCID
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2005-02-17
- Volume
- 93
- Issue
- 1
- Pages
- 84-93
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1998863653
- Cited by
- 52
- References
- 33
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 4 · 2021: 1 · 2020: 2 · 2019: 1 · 2017: 4 · 2016: 3 · 2014: 5 · 2013: 1 · 2012: 4
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer UK
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- pyruvate, monocarboxylate transporters, hydrogen peroxide, oxidative stress, neuronal cell death, neuroprotection, cortical neurons, cell viability
- MeSH terms
- Acrylates, Animals, Benzimidazoles, Carbon Isotopes, Cell Survival, Cells, Cultured, Cerebral Cortex, Dose-Response Relationship, Drug, Drug Interactions, Embryo, Mammalian, Glial Fibrillary Acidic Protein, Hydrogen Peroxide, Immunohistochemistry, Kinetics, Microtubule-Associated Proteins, Neurons, RNA, Messenger, Time Factors, Blotting, Northern, Blotting, Western, Cell Death, Gene Expression Regulation, Developmental, Pyruvic Acid, Inhibitory Concentration 50, Reverse Transcriptase Polymerase Chain Reaction, Monocarboxylic Acid Transporters, Rats
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