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Issue 12, 2017
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Oxidative stress-induced increase of intracellular zinc in astrocytes decreases their functional expression of P2X7 receptors and engulfing activity

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Abstract

Neuron–glia communication mediated by neuro- and glio-transmitters such as ATP and zinc is crucial for the maintenance of brain homeostasis, and its dysregulation is found under pathological conditions. It is reported that under oxidative stress-loaded conditions, astrocytes exhibit increased intra- and extra-cellular labile zinc, the latter triggering microglial M1 activation, while the pathophysiological role of the former remains unrevealed. In this study, we examined whether the oxidative stress-induced increase of intracellular labile zinc is involved in the P2X7 receptor (P2X7R)-mediated regulation of astrocytic engulfing activity. The exposure of cultured astrocytes to sub-lethal oxidative stress through their treatment with 400 μM H2O2 increased intracellular labile zinc, of which the concentration reached a peak level of approximately 2 μM at 2 h after the treatment. In astrocytes under sub-lethal oxidative stress, the uptake of YO-PRO-1 and latex beads as markers for P2X7R channel/pore activity and astrocytic engulfing activity, respectively, was decreased, and these decreased activities were accompanied by decreased expression of P2X7R at the plasma membrane via intracellular labile zinc-mediated translocation of it. With the oxidative stress, the expression level of full length P2X7R relative to that of its splice variants in astrocytes was decreased, leading to a decrease of the relative expression of the trimer consisting of full length P2X7R. Collectively, sub-lethal oxidative stress induces an astrocytic modal shift from the normal resting engulfing mode to the activated astrogliosis mode via an intracellular labile zinc-mediated decrease of the functional expression of P2X7R.

Graphical abstract: Oxidative stress-induced increase of intracellular zinc in astrocytes decreases their functional expression of P2X7 receptors and engulfing activity

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Publication details

The article was received on 05 Sep 2017, accepted on 22 Nov 2017 and first published on 01 Dec 2017


Article type: Paper
DOI: 10.1039/C7MT00257B
Citation: Metallomics, 2017,9, 1839-1851
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    Oxidative stress-induced increase of intracellular zinc in astrocytes decreases their functional expression of P2X7 receptors and engulfing activity

    T. Furuta, A. Mukai, A. Ohishi, K. Nishida and K. Nagasawa, Metallomics, 2017, 9, 1839
    DOI: 10.1039/C7MT00257B

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