title: Hypoosmotic swelling affects zinc homeostasis in cultured rat astrocytes.
abstract: Astrocyte swelling is observed in different types of brain injury including hepatic encephalopathy (HE). This study investigates the role of astrocyte swelling on Zn2+ homeostasis in hypoosmotically treated astrocytes by using the Zn2+ indicators Newport-Green, Zinquin, and RhodZin-3. Hypoosmolarity (205 mosmol/L) led to a persistent increase of the intracellular "free" Zn2+ concentration [Zn2+](i) within 15 min, which was reversible after reinstitution of normoosmolarity (305 mosmol/L). The hypoosmotic [Zn2+](i) increase was abolished in the presence of the Zn2+ 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 Zn2+ chelator TPEN. The data suggest that astrocyte swelling affects gene expression by modulation of [Zn2+](i). Whereas Zn2+-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.
authors: Clinic for Gastroenterology, Hepatology and Infectiology, Düsseldorf Heinrich-Heine University, Düsseldorf, Germany.
authors: Caroline
authors: C
authors: Kruczek
authors: Boris
authors: B
authors: Görg
authors: Verena
authors: V
authors: Keitel
authors: Elvis
authors: E
authors: Pirev
authors: Klaus D
authors: KD
authors: Kröncke
authors: Freimut
authors: F
authors: Schliess
authors: Dieter
authors: D
authors: Häussinger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000502:physiology*; D048429:Cell Size; D002478:Cells, Cultured; D006706:Homeostasis / Q000502:physiology*; D007424:Intracellular Fluid / Q000378:metabolism / Q000502:physiology; D009994:Osmolar Concentration; D009997:Osmotic Pressure / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000502:physiology*
chemical_list: D015032:Zinc