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Glycogen synthase kinase-3β mediates toll-like receptors 4/nuclear factor kappa-B-activated cerebral ischemia-reperfusion injury through regulation of fat mass and obesity-associated protein
BACKGROUND: Glycogen synthase kinase-3β (GSK3β), fat mass and obesity-associated protein (FTO), and toll-like receptors 4 (TLR4) take on critical significance in different biological processes, whereas their interactions remain unclear. The objective was the investigation of the interaction effect i...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer - Medknow
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679630/ https://www.ncbi.nlm.nih.gov/pubmed/38020949 http://dx.doi.org/10.4103/bc.bc_3_23 |
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author | Xu, Kaiwei Du, Wenwen Zhuang, Xiuxiu Liang, Dongdong Mo, Yunchang Wang, Junlu |
author_facet | Xu, Kaiwei Du, Wenwen Zhuang, Xiuxiu Liang, Dongdong Mo, Yunchang Wang, Junlu |
author_sort | Xu, Kaiwei |
collection | PubMed |
description | BACKGROUND: Glycogen synthase kinase-3β (GSK3β), fat mass and obesity-associated protein (FTO), and toll-like receptors 4 (TLR4) take on critical significance in different biological processes, whereas their interactions remain unclear. The objective was the investigation of the interaction effect in cerebral ischemia-reperfusion (I/R) injury. METHODS: The function of the cerebral cortex in the mouse middle cerebral artery occlusion (MCAO) model (each group n = 6) and P12 cells oxygen-glucose deprivation/reoxygenation (OGD/R) model was analyzed using short hairpin GSK3β lentivirus and overexpression of FTO lentivirus (in vitro), TLR4 inhibitor (TAK242), and LiCl to regulate GSK3β, FTO, TLR4 expression, and GSK3β activity, respectively. RESULTS: After GSK3β knockdown in the OGD/R model of PC12 cells, the levels of TLR4 and p-p65 were lower than in the control, and the level of FTO was higher than in the control. Knockdown GSK3β reversed the OGD/R-induced nuclear factor kappa-B transfer to the intranuclear nuclei. As indicated by the result, TLR4 expression was down-regulated by overexpressed FTO, and TLR4 expression was up-regulated notably after inhibition of FTO with the use of R-2HG. After the inhibition of the activity of GSK3β in vivo, the reduction of FTO in mice suffering from MCAO was reversed. CONCLUSIONS: Our research shows that GSK3β/FTO/TLR4 pathway contributes to cerebral I/R injury. |
format | Online Article Text |
id | pubmed-10679630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Wolters Kluwer - Medknow |
record_format | MEDLINE/PubMed |
spelling | pubmed-106796302023-09-27 Glycogen synthase kinase-3β mediates toll-like receptors 4/nuclear factor kappa-B-activated cerebral ischemia-reperfusion injury through regulation of fat mass and obesity-associated protein Xu, Kaiwei Du, Wenwen Zhuang, Xiuxiu Liang, Dongdong Mo, Yunchang Wang, Junlu Brain Circ Original Article BACKGROUND: Glycogen synthase kinase-3β (GSK3β), fat mass and obesity-associated protein (FTO), and toll-like receptors 4 (TLR4) take on critical significance in different biological processes, whereas their interactions remain unclear. The objective was the investigation of the interaction effect in cerebral ischemia-reperfusion (I/R) injury. METHODS: The function of the cerebral cortex in the mouse middle cerebral artery occlusion (MCAO) model (each group n = 6) and P12 cells oxygen-glucose deprivation/reoxygenation (OGD/R) model was analyzed using short hairpin GSK3β lentivirus and overexpression of FTO lentivirus (in vitro), TLR4 inhibitor (TAK242), and LiCl to regulate GSK3β, FTO, TLR4 expression, and GSK3β activity, respectively. RESULTS: After GSK3β knockdown in the OGD/R model of PC12 cells, the levels of TLR4 and p-p65 were lower than in the control, and the level of FTO was higher than in the control. Knockdown GSK3β reversed the OGD/R-induced nuclear factor kappa-B transfer to the intranuclear nuclei. As indicated by the result, TLR4 expression was down-regulated by overexpressed FTO, and TLR4 expression was up-regulated notably after inhibition of FTO with the use of R-2HG. After the inhibition of the activity of GSK3β in vivo, the reduction of FTO in mice suffering from MCAO was reversed. CONCLUSIONS: Our research shows that GSK3β/FTO/TLR4 pathway contributes to cerebral I/R injury. Wolters Kluwer - Medknow 2023-09-27 /pmc/articles/PMC10679630/ /pubmed/38020949 http://dx.doi.org/10.4103/bc.bc_3_23 Text en Copyright: © 2023 Brain Circulation https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Xu, Kaiwei Du, Wenwen Zhuang, Xiuxiu Liang, Dongdong Mo, Yunchang Wang, Junlu Glycogen synthase kinase-3β mediates toll-like receptors 4/nuclear factor kappa-B-activated cerebral ischemia-reperfusion injury through regulation of fat mass and obesity-associated protein |
title | Glycogen synthase kinase-3β mediates toll-like receptors 4/nuclear factor kappa-B-activated cerebral ischemia-reperfusion injury through regulation of fat mass and obesity-associated protein |
title_full | Glycogen synthase kinase-3β mediates toll-like receptors 4/nuclear factor kappa-B-activated cerebral ischemia-reperfusion injury through regulation of fat mass and obesity-associated protein |
title_fullStr | Glycogen synthase kinase-3β mediates toll-like receptors 4/nuclear factor kappa-B-activated cerebral ischemia-reperfusion injury through regulation of fat mass and obesity-associated protein |
title_full_unstemmed | Glycogen synthase kinase-3β mediates toll-like receptors 4/nuclear factor kappa-B-activated cerebral ischemia-reperfusion injury through regulation of fat mass and obesity-associated protein |
title_short | Glycogen synthase kinase-3β mediates toll-like receptors 4/nuclear factor kappa-B-activated cerebral ischemia-reperfusion injury through regulation of fat mass and obesity-associated protein |
title_sort | glycogen synthase kinase-3β mediates toll-like receptors 4/nuclear factor kappa-b-activated cerebral ischemia-reperfusion injury through regulation of fat mass and obesity-associated protein |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679630/ https://www.ncbi.nlm.nih.gov/pubmed/38020949 http://dx.doi.org/10.4103/bc.bc_3_23 |
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