PMID: 26412745

 

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Title : O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling

Abstract :

1. Apoptosis plays an important role in neural development and neurological disorders
2. In this study, we found that O-GlcNAcylation , a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad
3. By using co-immunoprecipitation and mutagenesis techniques, we identified O-GlcNAc modification at both Thr308 and Ser473 of AKT
4. O-GlcNAcylation-induced apoptosis was attenuated by over-expression of AKT
5. We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain
6. The elevation of O-GlcNAcylation coincided with activation of cell apoptosis
7. Finally, we found a negative correlation between AKT phosphorylation and O-GlcNAcylation in ischemic brain tissue
8. These results indicate that cerebral ischemia induces a rapid increase of O-GlcNAcylation that promotes apoptosis through down-regulation of AKT activity
9. These findings provide a novel mechanism through which O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling