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Kainic Acid-Induced Golgi Complex Fragmentation/Dispersal Shifts the Proteolysis of Reelin in Primary Rat Neuronal Cells: An In Vitro Model of Early Stage Epilepsy
The endoplasmic reticulum-lysosome-Golgi network plays an important role in Reelin glycosylation and its proteolytic processing. Golgi complex fragmentation is associated with the separation of Reelin from this network. Kainic acid (KA) is an excitotoxic agent commonly used to induce epilepsy in rod...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577368/ https://www.ncbi.nlm.nih.gov/pubmed/25790952 http://dx.doi.org/10.1007/s12035-015-9126-1 |
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author | Kaneko, Yuji Sullivan, Robert Dailey, Travis Vale, Fernando L. Tajiri, Naoki Borlongan, Cesar V. |
author_facet | Kaneko, Yuji Sullivan, Robert Dailey, Travis Vale, Fernando L. Tajiri, Naoki Borlongan, Cesar V. |
author_sort | Kaneko, Yuji |
collection | PubMed |
description | The endoplasmic reticulum-lysosome-Golgi network plays an important role in Reelin glycosylation and its proteolytic processing. Golgi complex fragmentation is associated with the separation of Reelin from this network. Kainic acid (KA) is an excitotoxic agent commonly used to induce epilepsy in rodents. The relationship between KA-induced neuronal damage and Golgi complex fragmentation has not been investigated, leaving a major gap in our understanding of the molecular mechanism underlying the development of pathophysiology in epilepsy. We cultured primary rat cortical neurons eitherin ambient condition (control) or treated with a range of KA doses to reveal whether Golgi complex fragmentation impaired neuronal function. The half-life maximal inhibitory concentration (IC (50)) value of KA was detected to be approximately 5 μM, whereby at these concentrations, KA impaired neuronal viability, which was closely associated with initial Golgi complex fragmentation and subsequent reduction in both the expression and glycosylation patterns of Reelin. These findings implicate that Golgi complex fragmentation and Reelin dysfunction are key contributors to neuronal cell death in the early stage of epilepsy pathophysiology, thereby representing as novel disease biomarkers, as well as potent therapeutic targets for epilepsy. |
format | Online Article Text |
id | pubmed-4577368 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-45773682016-04-05 Kainic Acid-Induced Golgi Complex Fragmentation/Dispersal Shifts the Proteolysis of Reelin in Primary Rat Neuronal Cells: An In Vitro Model of Early Stage Epilepsy Kaneko, Yuji Sullivan, Robert Dailey, Travis Vale, Fernando L. Tajiri, Naoki Borlongan, Cesar V. Mol Neurobiol Article The endoplasmic reticulum-lysosome-Golgi network plays an important role in Reelin glycosylation and its proteolytic processing. Golgi complex fragmentation is associated with the separation of Reelin from this network. Kainic acid (KA) is an excitotoxic agent commonly used to induce epilepsy in rodents. The relationship between KA-induced neuronal damage and Golgi complex fragmentation has not been investigated, leaving a major gap in our understanding of the molecular mechanism underlying the development of pathophysiology in epilepsy. We cultured primary rat cortical neurons eitherin ambient condition (control) or treated with a range of KA doses to reveal whether Golgi complex fragmentation impaired neuronal function. The half-life maximal inhibitory concentration (IC (50)) value of KA was detected to be approximately 5 μM, whereby at these concentrations, KA impaired neuronal viability, which was closely associated with initial Golgi complex fragmentation and subsequent reduction in both the expression and glycosylation patterns of Reelin. These findings implicate that Golgi complex fragmentation and Reelin dysfunction are key contributors to neuronal cell death in the early stage of epilepsy pathophysiology, thereby representing as novel disease biomarkers, as well as potent therapeutic targets for epilepsy. Springer US 2015-03-21 2016 /pmc/articles/PMC4577368/ /pubmed/25790952 http://dx.doi.org/10.1007/s12035-015-9126-1 Text en © The Author(s) 2015 https://creativecommons.org/licenses/by/4.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Article Kaneko, Yuji Sullivan, Robert Dailey, Travis Vale, Fernando L. Tajiri, Naoki Borlongan, Cesar V. Kainic Acid-Induced Golgi Complex Fragmentation/Dispersal Shifts the Proteolysis of Reelin in Primary Rat Neuronal Cells: An In Vitro Model of Early Stage Epilepsy |
title | Kainic Acid-Induced Golgi Complex Fragmentation/Dispersal Shifts the Proteolysis of Reelin in Primary Rat Neuronal Cells: An In Vitro Model of Early Stage Epilepsy |
title_full | Kainic Acid-Induced Golgi Complex Fragmentation/Dispersal Shifts the Proteolysis of Reelin in Primary Rat Neuronal Cells: An In Vitro Model of Early Stage Epilepsy |
title_fullStr | Kainic Acid-Induced Golgi Complex Fragmentation/Dispersal Shifts the Proteolysis of Reelin in Primary Rat Neuronal Cells: An In Vitro Model of Early Stage Epilepsy |
title_full_unstemmed | Kainic Acid-Induced Golgi Complex Fragmentation/Dispersal Shifts the Proteolysis of Reelin in Primary Rat Neuronal Cells: An In Vitro Model of Early Stage Epilepsy |
title_short | Kainic Acid-Induced Golgi Complex Fragmentation/Dispersal Shifts the Proteolysis of Reelin in Primary Rat Neuronal Cells: An In Vitro Model of Early Stage Epilepsy |
title_sort | kainic acid-induced golgi complex fragmentation/dispersal shifts the proteolysis of reelin in primary rat neuronal cells: an in vitro model of early stage epilepsy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577368/ https://www.ncbi.nlm.nih.gov/pubmed/25790952 http://dx.doi.org/10.1007/s12035-015-9126-1 |
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