Abstract: FR-PO624
Advanced Glycation End Products (AGEs) Interrupted Podocyte Autophagy Flux through mTOR Activation
Session Information
- Diabetes Mellitus and Obesity: Basic - Experimental - II
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
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