Nucleocytoplasmic p27Kip1 Export Is Required for ERK1/2-Mediated Reactive Astroglial Proliferation Following Status Epilepticus
Reactive astrogliosis is a prominent and ubiquitous reaction of astrocytes to many types of brain injury. Up-regulation of glial fibrillary acidic protein (GFAP) expression and astroglial proliferation are hallmarks of reactive astrogliosis. However, the mechanisms that regulate reactive astrogliosi...
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| Format: | Article |
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Frontiers Media S.A.
2018-06-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2018.00152/full |
| _version_ | 1818997984474431488 |
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| author | Ji-Eun Kim Tae-Cheon Kang |
| author_facet | Ji-Eun Kim Tae-Cheon Kang |
| author_sort | Ji-Eun Kim |
| collection | DOAJ |
| description | Reactive astrogliosis is a prominent and ubiquitous reaction of astrocytes to many types of brain injury. Up-regulation of glial fibrillary acidic protein (GFAP) expression and astroglial proliferation are hallmarks of reactive astrogliosis. However, the mechanisms that regulate reactive astrogliosis remain elusive. In the present study, status epilepticus (SE, a prolonged seizure activity) led to reactive astrogliosis showing the increases in GFAP expression and the number of proliferating astrocytes with prolonged extracellular signal receptor-activated kinases 1/2 (ERK1/2) activation and reduced nuclear p27Kip1 level. U0126, an ERK1/2 inhibitor, showed opposite effects. Leptomycin B (LMB), an inhibitor of chromosomal maintenance 1 (CRM1), attenuated nucleocytoplasmic p27Kip1 export and astroglial proliferation, although it up-regulated ERK1/2 phosphorylation and GFAP expression. Roscovitine ameliorated the reduced nuclear p27Kip1 level and astroglial proliferation without changing GFAP expression and ERK1/2 phosphorylation. U0126 aggravated SE-induced astroglial apoptosis in the molecular layer of the dentate gyrus that was unaffected by LMB and roscovitine. In addition, U0126 exacerbated SE-induced neuronal death, while LMB mitigated it. Roscovitine did not affect SE-induced neuronal death. The present data elucidate for the first time the roles of nucleocytoplasmic p27Kip1 transport in ERK1/2-mediated reactive astrogliosis independent of SE-induced neuronal death and astroglial apoptosis. Therefore, our findings suggest that nucleocytoplasmic p27Kip1 export may be required for ERK1/2-mediated astroglial proliferation during reactive astrogliosis, and that nuclear p27Kip1 entrapment may be a potential therapeutic strategy for anti-proliferation in reactive astrocytes. |
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| language | English |
| last_indexed | 2024-12-20T21:54:19Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-2f5ceb0e69054e9da0dba30448e6c09b2022-12-21T19:25:28ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-06-011210.3389/fncel.2018.00152372466Nucleocytoplasmic p27Kip1 Export Is Required for ERK1/2-Mediated Reactive Astroglial Proliferation Following Status EpilepticusJi-Eun KimTae-Cheon KangReactive astrogliosis is a prominent and ubiquitous reaction of astrocytes to many types of brain injury. Up-regulation of glial fibrillary acidic protein (GFAP) expression and astroglial proliferation are hallmarks of reactive astrogliosis. However, the mechanisms that regulate reactive astrogliosis remain elusive. In the present study, status epilepticus (SE, a prolonged seizure activity) led to reactive astrogliosis showing the increases in GFAP expression and the number of proliferating astrocytes with prolonged extracellular signal receptor-activated kinases 1/2 (ERK1/2) activation and reduced nuclear p27Kip1 level. U0126, an ERK1/2 inhibitor, showed opposite effects. Leptomycin B (LMB), an inhibitor of chromosomal maintenance 1 (CRM1), attenuated nucleocytoplasmic p27Kip1 export and astroglial proliferation, although it up-regulated ERK1/2 phosphorylation and GFAP expression. Roscovitine ameliorated the reduced nuclear p27Kip1 level and astroglial proliferation without changing GFAP expression and ERK1/2 phosphorylation. U0126 aggravated SE-induced astroglial apoptosis in the molecular layer of the dentate gyrus that was unaffected by LMB and roscovitine. In addition, U0126 exacerbated SE-induced neuronal death, while LMB mitigated it. Roscovitine did not affect SE-induced neuronal death. The present data elucidate for the first time the roles of nucleocytoplasmic p27Kip1 transport in ERK1/2-mediated reactive astrogliosis independent of SE-induced neuronal death and astroglial apoptosis. Therefore, our findings suggest that nucleocytoplasmic p27Kip1 export may be required for ERK1/2-mediated astroglial proliferation during reactive astrogliosis, and that nuclear p27Kip1 entrapment may be a potential therapeutic strategy for anti-proliferation in reactive astrocytes.https://www.frontiersin.org/article/10.3389/fncel.2018.00152/fullCRM1epilepsyKi-67LMBseizureU0126 |
| spellingShingle | Ji-Eun Kim Tae-Cheon Kang Nucleocytoplasmic p27Kip1 Export Is Required for ERK1/2-Mediated Reactive Astroglial Proliferation Following Status Epilepticus Frontiers in Cellular Neuroscience CRM1 epilepsy Ki-67 LMB seizure U0126 |
| title | Nucleocytoplasmic p27Kip1 Export Is Required for ERK1/2-Mediated Reactive Astroglial Proliferation Following Status Epilepticus |
| title_full | Nucleocytoplasmic p27Kip1 Export Is Required for ERK1/2-Mediated Reactive Astroglial Proliferation Following Status Epilepticus |
| title_fullStr | Nucleocytoplasmic p27Kip1 Export Is Required for ERK1/2-Mediated Reactive Astroglial Proliferation Following Status Epilepticus |
| title_full_unstemmed | Nucleocytoplasmic p27Kip1 Export Is Required for ERK1/2-Mediated Reactive Astroglial Proliferation Following Status Epilepticus |
| title_short | Nucleocytoplasmic p27Kip1 Export Is Required for ERK1/2-Mediated Reactive Astroglial Proliferation Following Status Epilepticus |
| title_sort | nucleocytoplasmic p27kip1 export is required for erk1 2 mediated reactive astroglial proliferation following status epilepticus |
| topic | CRM1 epilepsy Ki-67 LMB seizure U0126 |
| url | https://www.frontiersin.org/article/10.3389/fncel.2018.00152/full |
| work_keys_str_mv | AT jieunkim nucleocytoplasmicp27kip1exportisrequiredforerk12mediatedreactiveastroglialproliferationfollowingstatusepilepticus AT taecheonkang nucleocytoplasmicp27kip1exportisrequiredforerk12mediatedreactiveastroglialproliferationfollowingstatusepilepticus |