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Formate generated by cellular oxidation of formaldehyde accelerates the glycolytic flux in cultured astrocytes

Authors

  • Ketki Tulpule,

    1. Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany
    2. Centre for Environmental Research and Sustainable Technology, Leobener Strasse, Bremen, Germany
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  • Ralf Dringen

    Corresponding author
    1. Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany
    2. Centre for Environmental Research and Sustainable Technology, Leobener Strasse, Bremen, Germany
    3. School of Psychology and Psychiatry, Monash University, Clayton, Victoria, Australia
    • Centre for Biomolecular Interactions Bremen, University of Bremen, PO. Box 330440, D-28334 Bremen, Germany
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Abstract

Formaldehyde is a neurotoxic compound that can be endogenously generated in the brain. Because astrocytes play a key role in metabolism and detoxification processes in brain, we have investigated the capacity of these cells to metabolize formaldehyde using primary astrocyte-rich cultures as a model system. Application of formaldehyde to these cultures resulted in the appearance of formate in cells and in a time-, concentration- and temperature-dependent disappearance of formaldehyde from the medium that was accompanied by a matching extracellular accumulation of formate. This formaldehyde-oxidizing capacity of astrocyte cultures is likely to be catalyzed by alcohol dehydrogenase 3 and aldehyde dehydrogenase 2, because the cells of the cultures contain the mRNAs of these formaldehyde-oxidizing enzymes. In addition, exposure to formaldehyde increased both glucose consumption and lactate production by the cells. Both the strong increase in the cellular formate content and the increase in glycolytic flux were only observed after application of formaldehyde to the cells, but not after treatment with exogenous methanol or formate. The accelerated lactate production was not additive to that obtained for azide, a known inhibitor of complex IV of the respiratory chain, and persisted after removal of formaldehyde after a formaldehyde exposure for 1.5 h. These data demonstrate that cultured astrocytes efficiently oxidize formaldehyde to formate, which subsequently enhances glycolytic flux, most likely by inhibition of mitochondrial respiration. © 2012 Wiley Periodicals, Inc.

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