Suppression of nucleocytoplasmic p27Kip1 export attenuates CDK4-mediated neuronal death induced by status epilepticus. (July 2018)

• Record Type: Journal Article
• Authors: Kim, Ji-Eun; Kang, Tae-Cheon
• Is Part Of: Neuroscience research. Volume 132(2018)
• Page Start: 46
• Page End: 52
• Publication Date: 2018-07
• Subjects: CDK5 -- Epilepsy -- Flavopiridol -- Leptomycin B -- Seizure; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2017.10.001
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: Most of TUNEL-positive neurons showed CDK4 expression following SE. CDK5 inhibitors did not affected SE-induced neuronal death and CDK4 expression. Flavopiridol attenuated TUNEL signal and CDK4 expression induced by SE. Flavopiridol and LMB inhibited nuclear p27 Kip1 export and CDK4 induction. Suppression of nuclear p27 Kip1 release may attenuate CDK4-mediated neuronal death. 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 p27 Kip1 (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 p27 Kip1 translocation. These findings suggest that SE may lead to nucleocytoplasmic p27 Kip1 export that initiates CDK4, not CDK5, induction, which an abortive and fatal cell cycle re-entry progress in CA1 neurons.