Apoptosis in Ca<sup>2</sup> + reperfusion injury of cultured astrocytes: roles of reactive oxygen species and NF‐κB activation
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<jats:title>Abstract</jats:title><jats:p>We previously reported that incubation of cultured astrocytes in Ca<jats:sup>2</jats:sup> + ‐containing medium after exposure to Ca<jats:sup>2</jats:sup> + ‐free medium caused Ca<jats:sup>2</jats:sup> + influx followed by delayed cell death. Here, we studied the mechanisms underlying the Ca<jats:sup>2</jats:sup> + ‐mediated injury of cultured astrocytes. Our results show that Ca<jats:sup>2</jats:sup> + reperfusion injury of astrocytes appears to be mediated by apoptosis, as demonstrated by DNA fragmentation and prevention of death by caspase‐3 inhibitors. Paradoxical Ca<jats:sup>2</jats:sup> + challenge stimulated rapidly reactive oxygen species (ROS) production. Ca<jats:sup>2</jats:sup> + reperfusion injury of astrocytes was influenced by several reagents which modified ROS production. When astrocytes were exposed to hydrogen peroxide (H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>) for 30 min and then incubated without H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> for 1–5 days, cell toxicity including apoptosis was observed. Ca<jats:sup>2</jats:sup> + reperfusion injury induced by Ca<jats:sup>2</jats:sup> + depletion or H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> exposure was blocked by the iron chelator 1,10‐phenanthroline, the NF‐κB inhibitor pyrrolidinedithiocarbamate and the calcineurin inhibitor FK506. Incubation in normal medium after H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> exposure rapidly increased the level of nuclear NF‐κB p65 subunit, and the effect was blocked by 1,10‐phenanthroline, pyrrolidinedithiocarbamate and FK506. These findings indicate that Ca<jats:sup>2</jats:sup> + reperfusion‐induced apoptosis is mediated at least partly by ROS production and ROS cause NF‐κB activation in cultured astrocytes.</jats:p>
収録刊行物
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- European Journal of Neuroscience
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European Journal of Neuroscience 11 (12), 4204-4212, 1999-12
Wiley
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詳細情報
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- CRID
- 1361699995977303552
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- NII論文ID
- 30014381406
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- ISSN
- 14609568
- 0953816X
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- データソース種別
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