title: Gap junctions contribute to astrocytic resistance against zinc toxicity.
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.
authors: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 162-1 Songdo-dong, Yeonsu-gu, Inchon 406-840, Republic of Korea. jinulee@yonsei.ac.kr
authors: Jinu
authors: J
authors: Lee
authors: Yeong Shin
authors: YS
authors: Yim
authors: Suk Jin
authors: SJ
authors: Ko
authors: Dong Goo
authors: DG
authors: Kim
authors: Chul Hoon
authors: CH
authors: Kim
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D017629:Gap Junctions / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D015032:Zinc / Q000633:toxicity*
chemical_list: D018031:Connexin 43; C119129:18alpha-glycyrrhetinic acid; D016718:Arachidonic Acid; D015032:Zinc; D006034:Glycyrrhetinic Acid