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O-GlcNAcylation Reduces Ischemia-Reperfusion–Induced Brain Injury
O-GlcNAcylation is a common posttranslational modification of nucleocytoplasmic proteins with β-N-acetylglucosamine (GlcNAc) and regulates numerous biological processes. By using mouse models of cerebral ischemia induced by permanent and transient middle cerebral artery occlusion (MCAO), we observed...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587588/ https://www.ncbi.nlm.nih.gov/pubmed/28878265 http://dx.doi.org/10.1038/s41598-017-10635-0 |
Sumario: | O-GlcNAcylation is a common posttranslational modification of nucleocytoplasmic proteins with β-N-acetylglucosamine (GlcNAc) and regulates numerous biological processes. By using mouse models of cerebral ischemia induced by permanent and transient middle cerebral artery occlusion (MCAO), we observed an initial elevation (~1.7-fold, 1–4 hours after ischemia) and then decline of O-GlcNAcylation during cerebral ischemia. We found that moderate increase (<3-fold) of brain O-GlcNAcylation by pharmacological means ameliorated cerebral ischemia-reperfusion injury and the consequent motor and neurological deficits. Interference of the transient elevation of O-GlcNAcylation pharmacologically or genetically aggravates the ischemia-induced brain damage, motor deficits and mortality. The alteration of O-GlcNAcylation was also seen in the ischemic areas of postmortem human brains. This study reveals an important regulation of cerebral ischemia-reperfusion injury by O-GlcNAcylation and also provides a possible therapeutic strategy, i.e., by increasing O-GlcNAcylation, to reduce the cerebral damage and improve the clinical outcome of ischemic stroke. |
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