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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...

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Autores principales: Li, Yixin, Zhu, Jin, Liu, Yuanling, Chen, Xi, Lei, Shipeng, Li, Lingyu, Jiang, Beibei, Tan, Li, Yu, Shanshan, Zhao, Yong
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
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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.
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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
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