Formaldehyde stimulates Mrp1-mediated glutathione deprivation of cultured astrocytes

Authors

  • Ketki Tulpule,

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

    1. Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany
    2. Centre for Environmental Research and Sustainable Technology, Bremen, Germany
    3. School of Psychology and Psychiatry, Monash University, Clayton, Vic., Australia
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Address correspondence and reprint requests to Ralf Dringen, Centre for Biomolecular Interactions Bremen, University of Bremen, P.O. Box 330440, D-28334 Bremen, Germany. E-mail: ralf.dringen@uni-bremen.de

Abstract

J. Neurochem. (2011) 116, 626–635.

Abstract

Formaldehyde (Fal) is an environmental neurotoxin that is also endogenously produced in brain. Since the tripeptide glutathione (GSH) plays an important role in detoxification processes in brain cells, we have investigated the consequences of a Fal exposure on the GSH metabolism of brain cells, using astrocyte-rich primary cultures as model system. Treatment of these cultures with Fal resulted in a rapid time- and concentration-dependent depletion of cellular GSH and a matching increase in the extracellular GSH content. Exposure of astrocytes to 1 mm Fal for 3 h did not compromise cell viability but almost completely deprived the cells of GSH. Half-maximal deprivation of cellular GSH was observed after application of 0.3 mm Fal. This effect was rather specific for Fal, since methanol, formate or acetaldehyde did not affect cellular GSH levels. The Fal-stimulated GSH loss from viable astrocytes was completely prevented by semicarbazide-mediated chemical removal of Fal or by the application of MK571, an inhibitor of the multidrug resistance protein 1. These data demonstrate that Fal deprives astrocytes of cellular GSH by a multidrug resistance protein 1-mediated process.

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