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Arsenate Stimulates Glutathione Export from Viable Cultured Rat Cerebellar Granule Neurons

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Abstract

Arsenate is an environmental pollutant which contaminates the drinking water of millions of people worldwide. Numerous in vitro studies have investigated the toxicity of arsenate for a large number of different cell types. However, despite the known neurotoxic potential of arsenicals, little is known so far about the consequences of an exposure of neurons to arsenate. To investigate acute effects of arsenate on the viability and the glutathione (GSH) metabolism of neurons, we have exposed primary rat cerebellar granule neuron cultures to arsenate. Incubation of neurons for up to 6 h with arsenate in concentrations of up to 10 mM did not acutely compromise the cell viability, although the cells accumulated substantial amounts of arsenate. However, exposure to arsenate caused a time- and concentration-dependent increase in the export of GSH from viable neurons with significant effects observed for arsenate in concentrations above 0.3 mM. The arsenate-induced stimulation of GSH export was abolished upon removal of arsenate and completely prevented by MK571, an inhibitor of the multidrug resistance protein 1. These results demonstrate that arsenate is not acutely toxic to neurons but can affect the neuronal GSH metabolism by stimulating GSH export.

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Acknowledgments

Michaela C. Hohnholt would like to thank the “Forschungsförderung” of the University of Bremen for financial support. The authors would also like to acknowledge Irina Keberlein for technical support.

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The authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, P.O. Box 330440, 28334, Bremen, Germany

    Michaela C. Hohnholt, Eva-Maria Blumrich, Yvonne Koehler & Ralf Dringen

  2. Centre for Environmental Research and Sustainable Technology, University of Bremen, Bremen, Germany

    Michaela C. Hohnholt, Eva-Maria Blumrich, Yvonne Koehler & Ralf Dringen

  3. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2 Universitetsparken, 2100, Copenhagen, Denmark

    Michaela C. Hohnholt

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  1. Michaela C. Hohnholt
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Hohnholt, M.C., Blumrich, EM., Koehler, Y. et al. Arsenate Stimulates Glutathione Export from Viable Cultured Rat Cerebellar Granule Neurons. Neurochem Res 40, 561–571 (2015). https://doi.org/10.1007/s11064-014-1501-1

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