Inhibition of the Proteasome Regulator PA28 Aggravates Oxidized Protein Overload in the Diabetic Rat Brain

Oxidized protein overloading caused by diabetes is one accelerating pathological pathway in diabetic encephalopathy development. To determine whether the PA28-regulated function of the proteasome plays a role in diabetes-induced oxidative damaged protein degradation, brain PA28 alpha and PA28 beta interference experiments were performed in a high-fat diet (HFD) and streptozotocin (STZ)-induced rat model. The present results showed that proteasome activity was changed in the brains of diabetic rats, but the constitutive subunits were not. In vivo PA28 alpha and PA28 beta inhibition via adeno-associated virus (AAV) shRNA infection successfully decreased PA28 protein levels and further exacerbated oxidized proteins load by regulating proteasome catalytic activity. These findings suggest that the proteasome plays a role in the elimination of oxidized proteins and that PA28 is functionally involved in the regulation of proteasome activity in vivo. This study suggests that abnormal protein turbulence occurring in the diabetic brain could be explained by the proteasome-mediated degradation pathway. Changes in proteasome activity regulator PA28 could be a reason to induce oxidative aggregation in diabetic brain.

Automated summary

This study investigates the role of the PA28-regulated function of the proteasome in diabetes-induced oxidative damaged protein degradation. The results show that proteasome activity changes in the brains of diabetic rats and that PA28 is functionally involved in the regulation of proteasome activity. This suggests that abnormal protein turbulence in the diabetic brain could be explained by the proteasome-mediated degradation pathway.