Suppression of nucleocytoplasmic p27Kip1 export attenuates CDK4-mediated neuronal death induced by status epilepticus
- PMID: 29024678
- DOI: 10.1016/j.neures.2017.10.001
Suppression of nucleocytoplasmic p27Kip1 export attenuates CDK4-mediated neuronal death induced by status epilepticus
Abstract
Aberrant cell cycle re-entry promotes neuronal death in various neurological diseases. Thus, cyclin-dependent kinases (CDKs) seem to be one of potential therapeutic targets to prevent neuronal loss. In the present study, we investigated the involvements of CDK4, CDK5 and p27Kip1 (an endogenous CDK inhibitor) in status epilepticus (SE)-induced neuronal death. Following SE, CDK4 expression was increased in CA1 neurons, while CDK5 was decreased. Most of TUNEL-positive neurons showed CDK4 expression, but less CDK5 expression. Flavopiridol (a CDK4 inhibitor) attenuated TUNEL signal and CDK4 expression in CA1 neurons following SE. CDK5 inhibitors did not affect these phenomena. Both flavopiridol and leptomycin B (an inhibitor of chromosome region maintenance 1) mitigated SE-induced neuronal death by inhibiting nucleocytoplasmic p27Kip1 translocation. These findings suggest that SE may lead to nucleocytoplasmic p27Kip1 export that initiates CDK4, not CDK5, induction, which an abortive and fatal cell cycle re-entry progress in CA1 neurons.
Keywords: CDK5; Epilepsy; Flavopiridol; Leptomycin B; Seizure.
Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.
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