Enhanced Glutathione Efflux from Astrocytes in Culture by Low Extracellular Ca super(2+) and Curcumin

• Published in: Neurochemical research 2010-08, Vol.35 (8), p.1231-1238
• Main Authors: Stridh, Malin H, Correa, Fernando, Nodin, Christina, Weber, Stephen G, Blomstrand, Fredrik, Nilsson, Michael, Sandberg, Mats
• Format: Article
• Language: English
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-010-0179-2

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 (Ca super(2+) omission) GSH efflux from cultures of astroglial cells. Stimulated efflux of GSH was observed at medium concentration of 0, 0.1mM Ca super(2+), but not at 0.2 or 0.3mM Ca super(2+). Astroglia treated with 30 mu M 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 Ca super(2+)- omission was not affected by the P2X7-receptor antagonist Blue Brilliant G (100nM) or the pannexin mimetic/blocking peptide super(10)Panx1 but inhibited by the gap junction blocker carbenoxolone (100 mu M) and a hemichannel blocker Gap26 (300 mu M). 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.