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- Title
Apoptosis in Ca<sup>2</sup> + reperfusion injury of cultured astrocytes: roles of reactive oxygen species and NF-κB activation.
- Authors
Takuma, Kazuhiro; Lee, Eibai; Kidawara, Miyuki; Mori, Koichi; Kimura, Yuji; Baba, Akemichi; Matsuda, Toshio
- Abstract
Abstract We previously reported that incubation of cultured astrocytes in Ca2 + -containing medium after exposure to Ca2 + -free medium caused Ca2 + influx followed by delayed cell death. Here, we studied the mechanisms underlying the Ca2 + -mediated injury of cultured astrocytes. Our results show that Ca2 + reperfusion injury of astrocytes appears to be mediated by apoptosis, as demonstrated by DNA fragmentation and prevention of death by caspase-3 inhibitors. Paradoxical Ca2 + challenge stimulated rapidly reactive oxygen species (ROS) production. Ca2 + reperfusion injury of astrocytes was influenced by several reagents which modified ROS production. When astrocytes were exposed to hydrogen peroxide (H2O2) for 30 min and then incubated without H2O2 for 1–5 days, cell toxicity including apoptosis was observed. Ca2 + reperfusion injury induced by Ca2 + depletion or H2O2 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 H2O2 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 Ca2 + reperfusion-induced apoptosis is mediated at least partly by ROS production and ROS cause NF-κB activation in cultured astrocytes.
- Subjects
ASTROCYTES; APOPTOSIS; PHYSIOLOGICAL effects of calcium; PERFUSION; OXYGEN in the body
- Publication
European Journal of Neuroscience, 1999, Vol 11, Issue 12, p4204
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1046/j.1460-9568.1999.00850.x