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Calcineurin and mitochondrial function in glutamate‐induced neuronal cell death
Author(s) -
Ankarcrona Maria,
Dypbukt Jeannette M.,
Orrenius Sten,
Nicotera Pierluigi
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00959-3
Subject(s) - calcineurin , glutamate receptor , programmed cell death , apoptosis , biology , microbiology and biotechnology , mitochondrial permeability transition pore , nmda receptor , mitochondrion , necrosis , biochemistry , receptor , medicine , transplantation , genetics
We have previously reported that glutamate can trigger a succession of necrosis and apoptosis in cerebellar granule cells (CGC). Since specific blockers of the (NMDA) receptor channel prevented both types of cell death, the role of Ca 2+ ‐dependent processes in the initiation of glutamate toxicity was further investigated. We examined the possible involvement of mitochondria and the role of the Ca 2+ /calmodulin‐regulated protein phosphatase, calcineurin, in the development of either type of cell death. Cyclosporin A and the more selective calcineurin inhibitor, FK‐506, prevented the development of both early necrosis and delayed apoptosis. In addition, cyclosporin A prevented the collapse of mitochondrial membrane potential observed during the exposure to glutamate and the concomitant necrotic phase. When CsA was added immediately after glutamate removal, it also prevented delayed apoptosis of neurons that had survived the necrotic phase. Altogether, these results suggest the involvement of calcineurin and a role for mitochondrial deenergization as early signals in neuronal apoptosis induced by glutamate.