[Cell injury and its protection in astrocytes].
Incubation of cultured astrocytes in Ca(2+)-containing medium after exposure to Ca(2+)-free medium causes Ca2+ influx followed by delayed cell death. Here, we summarize the mechanisms underlying the Ca(2+)-mediated injury of cultured astrocytes and the protective effects of drugs against Ca(2+)-reperfusion injury. Our results show that Ca(2+)-reperfusion injury of astrocytes appears to be mediated by apoptosis as evidenced by DNA fragmentation and nuclear condensation. Calpain, reactive oxygen species (ROS) production, calcineurin, caspase-3, and NF-kappa B activation are involved in Ca(2+)-reperfusion injury. Several drugs including T-588 and idebenone protect astrocytes against Ca(2+)-reperfusion injury. The protective effect of idebenone is mediated by nerve growth factor production, whereas that of T-588 is mediated mainly by the mitogen-activated protein/extracellular signal-regulated kinase signal cascade.
Matsuda
T
T
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
Takuma
K
K
Lee
E
E
Baba
A
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D016227:Benzoquinones / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002154:Calpain / Q000494:pharmacology; D016923:Cell Death; D002478:Cells, Cultured; D006801:Humans; D015427:Reperfusion Injury / Q000473:pathology*; D014451:Ubiquinone / Q000031:analogs & derivatives
D016227:Benzoquinones; D014451:Ubiquinone; D002154:Calpain; C036619:idebenone; D002118:Calcium