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Gap junctions contribute to astrocytic resistance against zinc toxicity

Authors
 Jinu Lee  ;  Yeong Shin Yim  ;  Suk Jin Ko  ;  Dong Goo Kim  ;  Chul Hoon Kim 
Citation
 BRAIN RESEARCH BULLETIN, Vol.86(5-6) : 314-318, 2011 
Journal Title
BRAIN RESEARCH BULLETIN
ISSN
 0361-9230 
Issue Date
2011
MeSH
Animals ; Arachidonic Acid/pharmacology ; Astrocytes/cytology ; Astrocytes/drug effects* ; Astrocytes/metabolism* ; Cell Death/drug effects ; Cells, Cultured ; Connexin 43/genetics ; Connexin 43/metabolism ; Fluorescence Recovery After Photobleaching ; Gap Junctions/metabolism* ; Glycyrrhetinic Acid/analogs & derivatives ; Glycyrrhetinic Acid/pharmacology ; Hippocampus/cytology ; Humans ; Mice ; Zinc/toxicity*
Keywords
Zinc toxicity ; Astrocytes ; Gap junctions ; Connexin ; Arachidonic acid
Abstract
Astrocytic gap junctions have been implicated in the regulation of cell viability. High amounts of extracellular zinc, which is released during ischemia, seizure, and brain trauma, can be cytotoxic to astrocytes. We tested whether gap junction coupling between astrocytes plays an important role in modulating zinc toxicity in hippocampal astrocytes. Zinc induces cell death in a dose-dependent manner in primary cultured hippocampal astrocytes. Two gap junction inhibitors, 18β-glycyrrhetinic acid and arachidonic acid, had no effect on zinc-induced cell death in low-confluence culture, where physical separation prevents gap junctions from forming. However, these inhibitors can potentiate zinc toxicity in high-confluence astrocyte cultures. Zinc toxicity was substantially suppressed upon connexin 43 overexpression, whereas knockdown caused a significant enhancement of the toxicity in high-confluence cultures. These data suggest that gap junctions in hippocampal astrocytes provide a protective role against zinc toxicity.
Full Text
http://www.sciencedirect.com/science/article/pii/S0361923011002589
DOI
10.1016/j.brainresbull.2011.08.011
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Goo(김동구)
Kim, Chang Hoon(김창훈)
Yim, Yeong Shin(임영신)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/94684
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