Cargando…
Glycogen Synthase Kinase 3β Influences Injury Following Cerebral Ischemia/Reperfusion in Rats
Abnormal activation of GSK-3β is associated with psychiatric and neurodegenerative disorders. However, no study has examined the effect of GSK-3β on cerebral ischemia/reperfusion injury. We used oxygen-glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion (MCAO) as models of...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807413/ https://www.ncbi.nlm.nih.gov/pubmed/27019634 http://dx.doi.org/10.7150/ijbs.13918 |
_version_ | 1782423380006273024 |
---|---|
author | Li, Yixin Zhu, Jin Liu, Yuanling Chen, Xi Lei, Shipeng Li, Lingyu Jiang, Beibei Tan, Li Yu, Shanshan Zhao, Yong |
author_facet | Li, Yixin Zhu, Jin Liu, Yuanling Chen, Xi Lei, Shipeng Li, Lingyu Jiang, Beibei Tan, Li Yu, Shanshan Zhao, Yong |
author_sort | Li, Yixin |
collection | PubMed |
description | Abnormal activation of GSK-3β is associated with psychiatric and neurodegenerative disorders. However, no study has examined the effect of GSK-3β on cerebral ischemia/reperfusion injury. We used oxygen-glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion (MCAO) as models of ischemia/reperfusion in rats in vitro and in vivo. Our study showed that knockdown of GSK-3β with a GSK-3β siRNA virus improved injury and increased viability of neurons subjected to OGD/R. Levels of total Nrf2, nuclear Nrf2, and Nrf2 downstream proteins sulfiredoxin (Srx1) and thioredoxin (Trx1) increased after transfection with the GSK-3β siRNA virus. GSK-3β siRNA increased SOD activity and decreased MDA levels. Overexpression of GSK-3β with a pcDNA-GSK-3β virus showed opposite results. We also demonstrated that intracerebroventricular injection of GSK-3β siRNA in rats ameliorated neurological deficits, reduced brain infarct volume and water content, and reduced damage to cerebral cortical neurons after MCAO. Changes in total Nrf2, nuclear Nrf2, Srx1, Trx1, SOD, and MDA were similar to those observed in vitro. Our results show for the first time that GSK-3β can influence cerebral ischemia/reperfusion injury. The effects may be due to regulating the Nrf2/ARE pathway and decreasing oxidative stress. These results suggest a potential new drug target for clinical treatment of stroke. |
format | Online Article Text |
id | pubmed-4807413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-48074132016-03-25 Glycogen Synthase Kinase 3β Influences Injury Following Cerebral Ischemia/Reperfusion in Rats Li, Yixin Zhu, Jin Liu, Yuanling Chen, Xi Lei, Shipeng Li, Lingyu Jiang, Beibei Tan, Li Yu, Shanshan Zhao, Yong Int J Biol Sci Research Paper Abnormal activation of GSK-3β is associated with psychiatric and neurodegenerative disorders. However, no study has examined the effect of GSK-3β on cerebral ischemia/reperfusion injury. We used oxygen-glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion (MCAO) as models of ischemia/reperfusion in rats in vitro and in vivo. Our study showed that knockdown of GSK-3β with a GSK-3β siRNA virus improved injury and increased viability of neurons subjected to OGD/R. Levels of total Nrf2, nuclear Nrf2, and Nrf2 downstream proteins sulfiredoxin (Srx1) and thioredoxin (Trx1) increased after transfection with the GSK-3β siRNA virus. GSK-3β siRNA increased SOD activity and decreased MDA levels. Overexpression of GSK-3β with a pcDNA-GSK-3β virus showed opposite results. We also demonstrated that intracerebroventricular injection of GSK-3β siRNA in rats ameliorated neurological deficits, reduced brain infarct volume and water content, and reduced damage to cerebral cortical neurons after MCAO. Changes in total Nrf2, nuclear Nrf2, Srx1, Trx1, SOD, and MDA were similar to those observed in vitro. Our results show for the first time that GSK-3β can influence cerebral ischemia/reperfusion injury. The effects may be due to regulating the Nrf2/ARE pathway and decreasing oxidative stress. These results suggest a potential new drug target for clinical treatment of stroke. Ivyspring International Publisher 2016-02-29 /pmc/articles/PMC4807413/ /pubmed/27019634 http://dx.doi.org/10.7150/ijbs.13918 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. |
spellingShingle | Research Paper Li, Yixin Zhu, Jin Liu, Yuanling Chen, Xi Lei, Shipeng Li, Lingyu Jiang, Beibei Tan, Li Yu, Shanshan Zhao, Yong Glycogen Synthase Kinase 3β Influences Injury Following Cerebral Ischemia/Reperfusion in Rats |
title | Glycogen Synthase Kinase 3β Influences Injury Following Cerebral Ischemia/Reperfusion in Rats |
title_full | Glycogen Synthase Kinase 3β Influences Injury Following Cerebral Ischemia/Reperfusion in Rats |
title_fullStr | Glycogen Synthase Kinase 3β Influences Injury Following Cerebral Ischemia/Reperfusion in Rats |
title_full_unstemmed | Glycogen Synthase Kinase 3β Influences Injury Following Cerebral Ischemia/Reperfusion in Rats |
title_short | Glycogen Synthase Kinase 3β Influences Injury Following Cerebral Ischemia/Reperfusion in Rats |
title_sort | glycogen synthase kinase 3β influences injury following cerebral ischemia/reperfusion in rats |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807413/ https://www.ncbi.nlm.nih.gov/pubmed/27019634 http://dx.doi.org/10.7150/ijbs.13918 |
work_keys_str_mv | AT liyixin glycogensynthasekinase3binfluencesinjuryfollowingcerebralischemiareperfusioninrats AT zhujin glycogensynthasekinase3binfluencesinjuryfollowingcerebralischemiareperfusioninrats AT liuyuanling glycogensynthasekinase3binfluencesinjuryfollowingcerebralischemiareperfusioninrats AT chenxi glycogensynthasekinase3binfluencesinjuryfollowingcerebralischemiareperfusioninrats AT leishipeng glycogensynthasekinase3binfluencesinjuryfollowingcerebralischemiareperfusioninrats AT lilingyu glycogensynthasekinase3binfluencesinjuryfollowingcerebralischemiareperfusioninrats AT jiangbeibei glycogensynthasekinase3binfluencesinjuryfollowingcerebralischemiareperfusioninrats AT tanli glycogensynthasekinase3binfluencesinjuryfollowingcerebralischemiareperfusioninrats AT yushanshan glycogensynthasekinase3binfluencesinjuryfollowingcerebralischemiareperfusioninrats AT zhaoyong glycogensynthasekinase3binfluencesinjuryfollowingcerebralischemiareperfusioninrats |