Clioquinol inhibits zinc-triggered caspase activation in the hippocampal CA1 region of a global ischemic gerbil model.
BACKGROUND: Excessive release of chelatable zinc from excitatory synaptic vesicles is involved in the pathogenesis of selective neuronal cell death following transient forebrain ischemia. The present study was designed to examine the neuroprotective effect of a membrane-permeable zinc chelator, clio...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2912365?pdf=render |
| _version_ | 1818281361564237824 |
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| author | Tao Wang Wei Zheng He Xu Jia-Min Zhou Zhan-You Wang |
| author_facet | Tao Wang Wei Zheng He Xu Jia-Min Zhou Zhan-You Wang |
| author_sort | Tao Wang |
| collection | DOAJ |
| description | BACKGROUND: Excessive release of chelatable zinc from excitatory synaptic vesicles is involved in the pathogenesis of selective neuronal cell death following transient forebrain ischemia. The present study was designed to examine the neuroprotective effect of a membrane-permeable zinc chelator, clioquinol (CQ), in the CA1 region of the gerbil hippocampus after transient global ischemia. METHODOLOGY/PRINCIPAL FINDINGS: The common carotid arteries were occluded bilaterally, and CQ (10 mg/kg, i.p.) was injected into gerbils once a day. The zinc chelating effect of CQ was examined with TSQ fluorescence and autometallography. Neuronal death, the expression levels of caspases and apoptosis inducing factor (AIF) were evaluated using TUNEL, in situ hybridization and Western blotting, respectively. We were able to show for the first time that CQ treatment attenuates the ischemia-induced zinc accumulation in the CA1 pyramidal neurons, accompanied by less neuronal loss in the CA1 field of the hippocampus after ischemia. Furthermore, the expression levels of caspase-3, -9, and AIF were significantly decreased in the hippocampus of CQ-treated gerbils. CONCLUSIONS/SIGNIFICANCE: The present study indicates that the neuroprotective effect of CQ is related to downregulation of zinc-triggered caspase activation in the hippocampal CA1 region of gerbils with global ischemia. |
| first_indexed | 2024-12-13T00:03:54Z |
| format | Article |
| id | doaj.art-f73523c48bec4acd928cddd1b5d4f3c9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T00:03:54Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-f73523c48bec4acd928cddd1b5d4f3c92022-12-22T00:06:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0157e1188810.1371/journal.pone.0011888Clioquinol inhibits zinc-triggered caspase activation in the hippocampal CA1 region of a global ischemic gerbil model.Tao WangWei ZhengHe XuJia-Min ZhouZhan-You WangBACKGROUND: Excessive release of chelatable zinc from excitatory synaptic vesicles is involved in the pathogenesis of selective neuronal cell death following transient forebrain ischemia. The present study was designed to examine the neuroprotective effect of a membrane-permeable zinc chelator, clioquinol (CQ), in the CA1 region of the gerbil hippocampus after transient global ischemia. METHODOLOGY/PRINCIPAL FINDINGS: The common carotid arteries were occluded bilaterally, and CQ (10 mg/kg, i.p.) was injected into gerbils once a day. The zinc chelating effect of CQ was examined with TSQ fluorescence and autometallography. Neuronal death, the expression levels of caspases and apoptosis inducing factor (AIF) were evaluated using TUNEL, in situ hybridization and Western blotting, respectively. We were able to show for the first time that CQ treatment attenuates the ischemia-induced zinc accumulation in the CA1 pyramidal neurons, accompanied by less neuronal loss in the CA1 field of the hippocampus after ischemia. Furthermore, the expression levels of caspase-3, -9, and AIF were significantly decreased in the hippocampus of CQ-treated gerbils. CONCLUSIONS/SIGNIFICANCE: The present study indicates that the neuroprotective effect of CQ is related to downregulation of zinc-triggered caspase activation in the hippocampal CA1 region of gerbils with global ischemia.http://europepmc.org/articles/PMC2912365?pdf=render |
| spellingShingle | Tao Wang Wei Zheng He Xu Jia-Min Zhou Zhan-You Wang Clioquinol inhibits zinc-triggered caspase activation in the hippocampal CA1 region of a global ischemic gerbil model. PLoS ONE |
| title | Clioquinol inhibits zinc-triggered caspase activation in the hippocampal CA1 region of a global ischemic gerbil model. |
| title_full | Clioquinol inhibits zinc-triggered caspase activation in the hippocampal CA1 region of a global ischemic gerbil model. |
| title_fullStr | Clioquinol inhibits zinc-triggered caspase activation in the hippocampal CA1 region of a global ischemic gerbil model. |
| title_full_unstemmed | Clioquinol inhibits zinc-triggered caspase activation in the hippocampal CA1 region of a global ischemic gerbil model. |
| title_short | Clioquinol inhibits zinc-triggered caspase activation in the hippocampal CA1 region of a global ischemic gerbil model. |
| title_sort | clioquinol inhibits zinc triggered caspase activation in the hippocampal ca1 region of a global ischemic gerbil model |
| url | http://europepmc.org/articles/PMC2912365?pdf=render |
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