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Involvement of Calcineurin in Ca 2+ Paradox‐Like Injury of Cultured Rat Astrocytes
Author(s) -
Matsuda Toshio,
Takuma Kazuhiro,
Asano Shoichi,
Kishida Yoko,
Nakamura Hiroaki,
Mori Koichi,
Maeda Sadaaki,
Baba Akemichi
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70052004.x
Subject(s) - calcineurin , astrocyte , chemistry , neuroglia , neuroscience , microbiology and biotechnology , biophysics , biology , central nervous system , medicine , transplantation
The Ca 2+ /calmodulin‐dependent phosphatase calcineurin may have physiological and pathological roles in neurons, but little is known about the roles of the enzyme in glial cells. We have previously reported that reperfusion of cultured astrocytes in Ca 2+ ‐containing medium after exposure to Ca 2+ ‐free medium caused Ca 2+ influx followed by delayed cell death. In this study, we examined if calcineurin is involved in this Ca 2+ ‐mediated astrocytic injury. FK506, an inhibitor of calcineurin, protected cultured rat astrocytes against paradoxical Ca 2+ challenge‐induced injury in a dose‐dependent manner (10 −10 –10 −8 M ). Cyclosporin A at 1 µ M mimicked the effect of FK506. Rapamycin (1 µ M ) did not affect astrocyte injury, but it blocked the protective effect of FK506. Deltamethrin (20 n M ), another calcineurin inhibitor, had a similar protective effect, whereas okadaic acid did not. FK506 affected neither paradoxical Ca 2+ challenge‐induced increase in cytosolic Ca 2+ level nor Na + ‐Ca 2+ exchange activity in the cells, suggesting that the calcineurin is involved in processes downstream of increased cytosolic Ca 2+ level. Immunochemical studies showed that both calcineurin A (probably the Aβ2 isoform) and B subunits were expressed in the cells. It is concluded that calcineurin is present in cultured astrocytes and it has a pathological role in the cells.