ZnT-1 expression in astroglial cells protects against zinc toxicity and slows the accumulation of intracellular zinc [Erratum in: Glia. vol 48, pg 346, 2004]

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Title:	ZnT-1 expression in astroglial cells protects against zinc toxicity and slows the accumulation of intracellular zinc [Erratum in: Glia. vol 48, pg 346, 2004]
Creators Name:	Nolte, C., Gore, A., Sekler, I., Kresse, W., Hershfinkel, M., Hoffmann, A., Kettenmann, H. and Moran, A.
Abstract:	Zinc ions are emerging as an important factor in the etiology of neurodegenerative disorders and in brain damage resulting from ischemia or seizure activity. High intracellular levels of zinc are toxic not only to neurons but also to astrocytes, the major population of glial cells in the brain. In the present study, the role of ZnT-1 in reducing zinc-dependent cell damage in astrocytes was assessed. Zinc-dependent cell damage was apparent within 2 h of exposure to zinc, and occurred within a narrow range of ∼200 μM. Pretreatment with sublethal concentrations of zinc rendered astrocytes less sensitive to toxic zinc levels, indicating that preconditioning protects astrocytes from zinc toxicity. Fluorescence cell imaging revealed a steep reduction in intracellular zinc accumulation for the zinc-pretreated cells mediated by L-type calcium channels. Heterologous expression of ZnT-1 had similar effects; intracellular zinc accumulation was slowed down and the sensitivity of astrocytes to toxic zinc levels was reduced, indicating that this is specifically mediated by ZnT-1 expression. Immunohistochemical analysis demonstrated endogenous ZnT-1 expression in cultured astroglia, microglia, and oligodendrocytes. Pretreatment with zinc induced a 4-fold increase in the expression of the putative zinc transporter ZnT-1 in astroglia as shown by immunoblot analysis. The elevated ZnT-1 expression following zinc priming or after heterologous expression of ZnT-1 may explain the reduced zinc accumulation and the subsequent reduction in sensitivity toward toxic zinc levels. Induction of ZnT-1 may play a protective role when mild episodes of stroke or seizures are followed by a massive brain insult.
Keywords:	Astroglia, L-Type Calcium Channels, Transfection, Zinc Toxicity, Znt-1, Animals
Source:	Glia
ISSN:	0894-1491
Publisher:	Wiley
Volume:	48
Number:	2
Page Range:	145-155
Date:	17 September 2004
Official Publication:	https://doi.org/10.1002/glia.20065
PubMed:	View item in PubMed

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