Glutamate and the NO donor, nitroprusside, synergistically induced the death of B50 cells from a rat CNS-derived neuroblastoma cell line. With low [nitroprusside] (10μM) both nitroprusside and glutamate were required. Under these conditions, nuclei became pyknotic and caspases were activated. The activities of caspase-3 and caspase-6 (effector caspases) were higher than those of caspase-8 and caspase-9 (initiator caspases). The activation of all four caspases was inhibited by cyclosporin A, with the order of susceptibility caspase-8=caspase-9=caspase-6>caspase-3. To identify the possible locus of cyclosporin A action, we used an antisense oligodeoxynucleotide to suppress the level of cyclophilin-A to < 5% of its control value. Cyclophilin-A suppression largely reproduced the inhibitory effects of cyclosporin A. These results provide the first indication that cyclophilin-A participates in the activation of the caspase cascade in neuronal cells, in particular in the form of cascade elicited by excitotoxic stimuli. It is concluded that neuroprotection by cyclosporin A against excitotoxin-induced apoptosis is, at least partly, due to inhibition of cyclophilin-A.
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April 2002
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Research Article|
March 22 2002
Cyclophilin-A is involved in excitotoxin-induced caspase activation in rat neuronal B50 cells Available to Purchase
Michela CAPANO;
Michela CAPANO
Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, U.K.
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Sukaina VIRJI;
Sukaina VIRJI
Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, U.K.
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Martin CROMPTON
Martin CROMPTON
1
Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, U.K.
1To whom correspondence should be addressed (e-mail [email protected])
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Publisher: Portland Press Ltd
Received:
August 23 2001
Revision Received:
November 08 2001
Accepted:
January 18 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 363 (1): 29–36.
Article history
Received:
August 23 2001
Revision Received:
November 08 2001
Accepted:
January 18 2002
Citation
Michela CAPANO, Sukaina VIRJI, Martin CROMPTON; Cyclophilin-A is involved in excitotoxin-induced caspase activation in rat neuronal B50 cells. Biochem J 1 April 2002; 363 (1): 29–36. doi: https://doi.org/10.1042/bj3630029
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