Abstract: FR-PO624

Advanced Glycation End Products (AGEs) Interrupted Podocyte Autophagy Flux through mTOR Activation

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Zhao, Xingchen, Guangdong General Hosiptial, Guangzhou, China
  • Chen, Yuanhan, Guangdong General Hosiptial, Guangzhou, China
  • Liang, Xinling, Guangdong General Hosiptial, Guangzhou, China
  • Shi, Wei, Guangdong General Hosiptial, Guangzhou, China
Background

Insufficient podocyte autophagy exacerbates podocyte injury and renal dysfunction under diabetic conditions. AGEs are a classic pathogenic factors under diabetic conditions. In present study, we studied the role of AGEs on podocyte autophagy and its underlying mechanism.

Methods

Db/db mice were gavaged by Pyridoxamine(inhibitor of AGE formation) to mimic diabetic conditions with low- AGEs serum levels. Autophagy were examed by Western blotting, immunofluorescent staining, transmission electron microscopy.

Results

1. AGE inhibited podocyte autophagy and led to podocyte injury in vivo and in vitro (FIG 1A-D ).
2. We further found that AGE blocked autophagy flux via interfering the formation of autophagosme, fusion of autophasome and lysosome in cultured podocyte(FIG1 E-F).
3. mTOR is an important autophagy negative regulator. Next, we found AGE activated mTOR activity in vivo and in vitro. mTOR activation mediated AGE-induced podocyte autophagy inhibition in vivo and in vitro(FIG2).

Conclusion

AGE interrupted podocyte autophagy flux through mTOR activation.

FIG1 AGEs inhibited podocyte autophagy and led to podocyte injury in vivo and in vitro

FIG2 mTOR mediated AGE-reduced podocyte autophagy in vivo and in vitro