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Hypoosmotic swelling affects zinc homeostasis in cultured rat astrocytes
Author(s) -
Kruczek Caroline,
Görg Boris,
Keitel Verena,
Pirev Elvis,
Kröncke Klaus D.,
Schliess Freimut,
Häussinger Dieter
Publication year - 2008
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20737
Subject(s) - astrocyte , metallothionein , biology , downregulation and upregulation , nmda receptor , glutamate receptor , nitric oxide , microbiology and biotechnology , homeostasis , receptor , biochemistry , endocrinology , central nervous system , gene
Astrocyte swelling is observed in different types of brain injury including hepatic encephalopathy (HE). This study investigates the role of astrocyte swelling on Zn 2+ homeostasis in hypoosmotically treated astrocytes by using the Zn 2+ indicators Newport‐Green, Zinquin, and RhodZin‐3. Hypoosmolarity (205 mosmol/L) led to a persistent increase of the intracellular “free” Zn 2+ concentration [Zn 2+ ] i within 15 min, which was reversible after reinstitution of normoosmolarity (305 mosmol/L). The hypoosmotic [Zn 2+ ] i increase was abolished in the presence of the Zn 2+ chelator TPEN, the NMDA receptor antagonists MK‐801 and AP5, the antioxidant epigallocatechin gallate, and the nitric oxide synthase inhibitors L ‐NMMA and TRIM. Hypoosmolarity triggered nuclear accumulation of the metal response element‐binding transcription factor MTF‐1 and the specificity protein Sp1 and expression of the mRNAs encoding metallothionein and the Sp1‐regulated peripheral‐type benzodiazepine receptor (PBR). These effects were abolished by the Zn 2+ chelator TPEN. The data suggest that astrocyte swelling affects gene expression by modulation of [Zn 2+ ] i . Whereas Zn 2+ ‐dependent upregulation of metallothionein may help to counteract excessive astrocyte swelling and production of reactive oxygen and nitrogen oxide species, stimulation of PBR expression may augment HE development. © 2008 Wiley‐Liss, Inc.