Hypoosmotic swelling affects zinc homeostasis in cultured rat astrocytes.
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.
Kruczek
Caroline
C
Clinic for Gastroenterology, Hepatology and Infectiology, Düsseldorf Heinrich-Heine University, Düsseldorf, Germany.
Görg
Boris
B
Keitel
Verena
V
Pirev
Elvis
E
Kröncke
Klaus D
KD
Schliess
Freimut
F
Häussinger
Dieter
D
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*
D015032:Zinc