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  • 标题:O-GlcNAcylation Reduces Ischemia-Reperfusion–Induced Brain Injury
  • 本地全文:下载
  • 作者:Jin-hua Gu ; Jianhua Shi ; Chun-ling Dai
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2017
  • 卷号:7
  • 期号:1
  • DOI:10.1038/s41598-017-10635-0
  • 语种:English
  • 出版社:Springer Nature
  • 摘要: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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