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Inhibiting Caspase-12 Mediated Inflammasome Activation protects against Oxygen-Glucose Deprivation Injury in Primary Astrocytes
Stroke is one of the leading causes of death worldwide. Accumulating evidence suggests that NLRP3 inflammasome activation plays an important role in ischemic stroke injury. However, the existence of the NLRP3 inflammasome in astrocytes remains controversial. In this study, we demonstrated the presen...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415396/ https://www.ncbi.nlm.nih.gov/pubmed/32788872 http://dx.doi.org/10.7150/ijms.44330 |
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author | Liu, Lu Chen, Manli Lin, Kun Xiang, Xuwu Zheng, Yueying Zhu, Shengmei |
author_facet | Liu, Lu Chen, Manli Lin, Kun Xiang, Xuwu Zheng, Yueying Zhu, Shengmei |
author_sort | Liu, Lu |
collection | PubMed |
description | Stroke is one of the leading causes of death worldwide. Accumulating evidence suggests that NLRP3 inflammasome activation plays an important role in ischemic stroke injury. However, the existence of the NLRP3 inflammasome in astrocytes remains controversial. In this study, we demonstrated the presence of the NLRP3 inflammasome in primary mouse astrocytes and investigated the role of caspase-12 in NLRP3 inflammasome activation and cell injury in an in vitro astrocyte oxygen-glucose deprivation (OGD) model. Astrocytes exposed to 2, 3, and 4 h of OGD exhibited increased cell injury and apoptosis, and the protein levels of caspase-12, cleaved caspase-3, NLRP3 inflammasome components, and IL-1β were also significantly elevated. Interestingly, pretreatment with the caspase-12-specific inhibitor Z-ATAD-FMK attenuated cell injury and apoptosis and decreased the levels of NLRP3, caspase-1, IL-1β, and cleaved caspase-3 in the OGD group. In conclusion, Z-ATAD-FMK protected astrocytes against OGD-induced cell death and inhibited NLPR3-inflammasome activation. Our results indicate that caspase-12 and its potential regulation of NLRP3 inflammasome activation might be a promising target for treatment of ischemic stroke. |
format | Online Article Text |
id | pubmed-7415396 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-74153962020-08-11 Inhibiting Caspase-12 Mediated Inflammasome Activation protects against Oxygen-Glucose Deprivation Injury in Primary Astrocytes Liu, Lu Chen, Manli Lin, Kun Xiang, Xuwu Zheng, Yueying Zhu, Shengmei Int J Med Sci Research Paper Stroke is one of the leading causes of death worldwide. Accumulating evidence suggests that NLRP3 inflammasome activation plays an important role in ischemic stroke injury. However, the existence of the NLRP3 inflammasome in astrocytes remains controversial. In this study, we demonstrated the presence of the NLRP3 inflammasome in primary mouse astrocytes and investigated the role of caspase-12 in NLRP3 inflammasome activation and cell injury in an in vitro astrocyte oxygen-glucose deprivation (OGD) model. Astrocytes exposed to 2, 3, and 4 h of OGD exhibited increased cell injury and apoptosis, and the protein levels of caspase-12, cleaved caspase-3, NLRP3 inflammasome components, and IL-1β were also significantly elevated. Interestingly, pretreatment with the caspase-12-specific inhibitor Z-ATAD-FMK attenuated cell injury and apoptosis and decreased the levels of NLRP3, caspase-1, IL-1β, and cleaved caspase-3 in the OGD group. In conclusion, Z-ATAD-FMK protected astrocytes against OGD-induced cell death and inhibited NLPR3-inflammasome activation. Our results indicate that caspase-12 and its potential regulation of NLRP3 inflammasome activation might be a promising target for treatment of ischemic stroke. Ivyspring International Publisher 2020-07-19 /pmc/articles/PMC7415396/ /pubmed/32788872 http://dx.doi.org/10.7150/ijms.44330 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Liu, Lu Chen, Manli Lin, Kun Xiang, Xuwu Zheng, Yueying Zhu, Shengmei Inhibiting Caspase-12 Mediated Inflammasome Activation protects against Oxygen-Glucose Deprivation Injury in Primary Astrocytes |
title | Inhibiting Caspase-12 Mediated Inflammasome Activation protects against Oxygen-Glucose Deprivation Injury in Primary Astrocytes |
title_full | Inhibiting Caspase-12 Mediated Inflammasome Activation protects against Oxygen-Glucose Deprivation Injury in Primary Astrocytes |
title_fullStr | Inhibiting Caspase-12 Mediated Inflammasome Activation protects against Oxygen-Glucose Deprivation Injury in Primary Astrocytes |
title_full_unstemmed | Inhibiting Caspase-12 Mediated Inflammasome Activation protects against Oxygen-Glucose Deprivation Injury in Primary Astrocytes |
title_short | Inhibiting Caspase-12 Mediated Inflammasome Activation protects against Oxygen-Glucose Deprivation Injury in Primary Astrocytes |
title_sort | inhibiting caspase-12 mediated inflammasome activation protects against oxygen-glucose deprivation injury in primary astrocytes |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415396/ https://www.ncbi.nlm.nih.gov/pubmed/32788872 http://dx.doi.org/10.7150/ijms.44330 |
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