High glucose increases podocyte autophagy through PI3K-AKT-mTOR signaling pathway
10.3760/cma.j.issn.1001-7097.2013.07.007
- VernacularTitle:高糖通过PI3K-AKT-mTOR信号通路增加足细胞自噬
- Author:
Jili ZHU
;
Tean MA
;
Xinghua CHEN
;
Qian YANG
;
Guohua DING
- Publication Type:Journal Article
- Keywords:
Glucose;
Podocytes;
Signal transduction;
Autophagy
- From:
Chinese Journal of Nephrology
2013;29(7):515-519
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effects of high glucose on autophagy and apoptosis of podocyte and explore the signaling pathway in high glucose-induce podocyte autophagy.Methods Differentiated mouse podocytes were exposed to high glucose(30 mmol/L) or rapamycin (autophagy enhancer,1 μg/L) or LY294002 (a selective PI3K inhibitor,50 mmol/L) for 24 h.The formations of autophagy were observed by electron microscopy and acridine orange staining.Apoptosis was evaluated by flow cytometry.The expression of autophagy protein LC3-Ⅱ/Ⅰ and Beclin-1 as well as the phosphorylation of AKT and mTOR were examined by Western blotting analysis.Results High glucose induced podocytes apoptosis,increased autophagy and the expression of autophagy-associated proteins (all P ＜ 0.05).Rapamycin further increased the expression of LC3-Ⅱ and Beclin-1 protein (all P ＜ 0.05),but LY294002 inhibited partialiy the protein expression of LC3-Ⅱ and Beclin-1 induced by high glucose (both P ＜ 0.05).Treatment with rapamycin increased the phosphorylation of AKT,but reduced that of mTOR in podocytes.Moreover,LY294002 inhibited phosphorylation of both AKT and mTOR (both P ＜ 0.05).Conclusions High glucose promotes podocyte autophagy and apoptosis.High glucose-induced autophagy is mediated partly through PI3K-AKT-mTOR signaling pathway.
