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

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• 作者：Liqun Ma ; Rongguo Fu ; Zhaoyang Duan ; Jiamei Lu ; Jie Gao ; Lifang Tian ; Zhian Lv ; Zhao Chen ; Jin Han ; Lining Jia ; Li Wang ; ^{wanglieryuan@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Diabetic nephropathy ; Sirt1 ; Resveratrol ; Autophagy ; Hypoxia
• 刊名：Pathology - Research and Practice
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：212
• 期：4
• 页码：310-318
• 全文大小：1905 K

文摘

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% O₂ 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.