Sirt1 is essential for resveratrol enhancement of hypoxia-induced autophagy in the type 2 diabetic nephropathy rat

被引：99

作者：

Ma, Liqun ^{[1
]}

Fu, Rongguo ^{[1
]}

Duan, Zhaoyang ^{[1
]}

Lu, Jiamei ^{[1
]}

Gao, Jie ^{[1
]}

Tian, Lifang ^{[1
]}

Lv, Zhian ^{[1
]}

Chen, Zhao ^{[1
]}

Han, Jin ^{[1
]}

Jia, Lining ^{[1
]}

Wang, Li ^{[1
]}

机构：

[1] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Nephrol, 157 Xiwu Rd, Xian 710004, Shaanxi Provinc, Peoples R China

来源：

PATHOLOGY RESEARCH AND PRACTICE | 2016年 / 212卷 / 04期

关键词：

Diabetic nephropathy; Sirt1; Resveratrol; Autophagy; Hypoxia; OXIDATIVE STRESS; INDUCIBLE FACTOR; CELL; RESTRICTION; DISEASE; KIDNEY; ACTIVATION; MECHANISM; PATHWAYS; SIRTUINS;

D O I：

10.1016/j.prp.2016.02.001

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Type 2 diabetic nephropathy (DN) is a serious end-stage kidney disease worldwide. Multiple studies demonstrate that resveratrol (RSV) has a beneficial effect on DN. However, whether RSV-induced improvement in kidney function in diabetes is due to the regulation of autophagy remains unclear. Here, we investigated the mechanisms underlying RSV-mediated protection against DN in diabetic rats, with a special focus on the role of NAD-dependent deacetylase sirtuin 1 (Sirt1) in regulating autophagy. We found that long-term RSV treatment in rats promoted Sirt1 expression and improved related metabolic levels in the diabetic kidney. Our study showed that, in cultured NRK-52E cells, Sirt1 knockdown inhibited the autophagy levels of proteins Atg7, Atg5, and LC3 and impaired the RSV amelioration of dysfunctional autophagy under hypoxic condition. Furthermore, exposed to 1% O-2 over time induced autophagy dysfunction and apoptosis in NRK-52E cells, which could be improved by RSV treatment. Our data highlight the role of the Sirt1-mediated pathway in the effects of RSV on autophagy in vivo and in vitro, suggesting RSV could be a potential new therapy for type 2 DN. (C) 2016 Elsevier GmbH. All rights reserved.

引用

页码：310 / 318

页数：9

共 40 条

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