PMID: 26412745

 

    Legend: Gene, Sites

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

Output (sent_index, trigger, protein, sugar, site):

Output(Part-Of) (sent_index, protein, site):

• 3. AKT, Thr308 and Ser473

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
AKT	11651	0,2,3,4,8,9