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Enhanced Glutathione Efflux from Astrocytes in Culture by Low Extracellular Ca2+ and Curcumin

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Abstract

Efflux of glutathione (GSH) from astrocytes has been suggested as a key factor for neuroprotection by astrocytes. Here we evaluated if the Nrf2 activator curcumin affects basal and stimulated (Ca2+ omission) GSH efflux from cultures of astroglial cells. Stimulated efflux of GSH was observed at medium concentration of 0, 0.1 mM Ca2+, but not at 0.2 or 0.3 mM Ca2+. Astroglia treated with 30 μM curcumin increased the cellular content of GSH in parallel with elevated basal and stimulated efflux. Conversely treatment with buthionine sulfoximine lowered efflux of GSH. The efflux stimulated by Ca2+- omission was not affected by the P2X7-receptor antagonist Blue Brilliant G (100 nM) or the pannexin mimetic/blocking peptide 10Panx1 but inhibited by the gap junction blocker carbenoxolone (100 μM) and a hemichannel blocker Gap26 (300 μM). RNAi directed against Nrf2 partly inhibited the effect of curcumin. The results show that elevated cellular GSH by curcumin treatment enhance efflux from astroglial cells, a process which appear to be a prerequisite for astroglial mediated neuroprotection.

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Acknowledgments

The work was supported by the Swedish Research Council/Medicine to MS, Parkinsonfonden and Åhlénstiftelsen. MS and SGW are supported by the National Institutes of Health (GM 44842). FB is supported by Fredrik and Ingrid Thurings-, Edit Jacobsons- and Magnus Bergvalls foundations. MN is supported by the Swedish Research Council, LUA/ALF, the region of West Sweden (RUN) and Edit Jacobssons Foundation.

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Authors and Affiliations

  1. Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden

    Malin H. Stridh, Christina Nodin, Fredrik Blomstrand, Michael Nilsson & Mats Sandberg

  2. Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

    Fernando Correa & Mats Sandberg

  3. Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Stephen G. Weber

  4. Abteilung für Allgemeine Zoologie, Fachbereich Biologie, Technische Universität Kaiserslautern, Erwin-Schrödinger-Straße 13, 67663, Kaiserslautern, Germany

    Malin H. Stridh

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  1. Malin H. Stridh
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  2. Fernando Correa
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  3. Christina Nodin
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  4. Stephen G. Weber
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  7. Mats Sandberg
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Correspondence to Malin H. Stridh.

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Stridh, M.H., Correa, F., Nodin, C. et al. Enhanced Glutathione Efflux from Astrocytes in Culture by Low Extracellular Ca2+ and Curcumin. Neurochem Res 35, 1231–1238 (2010). https://doi.org/10.1007/s11064-010-0179-2

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  • DOI: https://doi.org/10.1007/s11064-010-0179-2

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