inhibits neurodegeneration by downregulating O-GlcNAcylation of NF-κB in diabetic mice.

AIM

To investigate the role of O-GlcNAcylation of nuclear factor-kappa B (NF-κB) in retinal ganglion cell (RGC) death and analysedthe effect of (AE) on neurodegeneration in diabetic mice.

METHODS

C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control (CTL) diet at the onset of diabetes mellitus (DM). Two months after injection of streptozotocin or saline, the degree of cell death and the expression of O-GlcNAc transferase (OGT), N-acetyl-b-D-glucosaminidase (OGA), O-GlcNAcylated proteins, and O-GlcNAcylation of NF-κB were examined.

RESULTS

AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness (<0.001 CTL, <0.01 DM) and increases in RGCs with terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (<0.001 CTL, <0.0001 DM), glial activation, and active caspase-3 (<0.0001 CTL, <0.0001 DM) were blocked in diabetic retinas of AE extract-fed mice. Expression levels of protein O-GlcNAcylation and OGT were increased in diabetic retinas (<0.0001 CTL), and the level of O-GlcNAcylation of the NF-κB p65 subunit was higher in diabetic retinas than in controls (<0.0001 CTL). AE extract downregulated O-GlcNAcylation of NF-κB and prevented neurodegeneration induced by hyperglycemia (<0.0001 DM).

CONCLUSION

O-GlcNAcylation of NF-κB is concerned in neuronal degeneration and that AE prevents diabetes-induced RGC apoptosis downregulation of NF-κB O-GlcNAcylation. Hence, O-GlcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic possibility to prevent diabetes-induced neurodegeneration.