首页 / 院系成果 / 成果详情页

Sirt3 deficiency exacerbates diabetic cardiac dysfunction: Role of Foxo3A-Parkin-mediated mitophagy 期刊论文

编号：

218997ac-9268-40ea-bb7b-243e35e857b0
作者：

Yu, Wenjun^[1,2,3];Gao, Beilei^[1,3];Li, Na^[1,6];Wang, Jiaxing^[3,4];Qiu, Cuiting^[3];Zhang, Guoyong^[1,3];Liu, Min^[3];Zhang, Rongqing^[3];Li, Congye^[3];Ji, Gang^[5];Zhang, Yingmei*^[1,3]
语种：

English
期刊：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE ISSN：0925-4439 2017 年 1863 卷 8 期 (1973 - 1983) ; AUG
收录：
关键词：

Sirt3 Streptozotocin Cardiac function Foxo3A Parkin Mitophagy
摘要：

Diabetic cardiomyopathy (DCM) is often associated with suppressed cardiac autophagy, mitochondrial structural and functional impairment. Sirtuin-3 (Sirt3) has been reported to play a crucial role in mitochondrial homeostasis and confers a protective role against the onset and development of DCM although the precise mechanism(s) remains elusive. Here we hypothesized that Sirt3 exerts cardioprotection against DCM by activating Parkin-mediated mitophagy, en route to preserved mitochondrial homeostasis and suppressed cardiomyocyte apoptosis. Adult male wild-type (WT) and Sirt3 knockout (Sirt3KO) mice were treated with streptozotocin (STZ) or vehicle for 3 months prior to assessment of echocardiographic property, interstitial fibrosis, cardiomyocyte apoptosis, mitochondrial morphology, cardiac autophagy and cell signaling molecules. Our findings revealed that STZ-induced diabetes mellitus prompted cardiac dysfunction, interstitial fibrosis, cardiomyocyte apoptosis and mitochondrial injury, accompanied with suppressed autophagy and mitophagy, the effects of which were aggravated by Sirt3KO. To the contrary, Sirt3 overexpression in vitro activated autophagy and mitophagy, inhibited mitochondrial injury and cardiomyocyte apoptosis, the effects of which were attenuated by autophagy inhibition using 3-MA. Moreover, deacetylation of Foxo3A and expression of Parkin were decreased by Sirt3KO, while these effects were facilitated by Sirt3OE in diabetic and high glucose settings. Taken together, our data suggested that suppressed Sirt3-Foxo3A-Parkin signaling mediated downregulation of mitophagy may play a vital role in the development of diabetic cardiomyopathy. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure edited by Dr. Jun Ren & Yingmei Zhang. (C) 2016 Published by Elsevier B.V.
推荐引用方式
GB/T 7714：

Yu Wenjun,Gao Beilei,Li Na, et al. Sirt3 deficiency exacerbates diabetic cardiac dysfunction: Role of Foxo3A-Parkin-mediated mitophagy [J].BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,2017,1863(8):1973-1983.
APA：

Yu Wenjun,Gao Beilei,Li Na,Wang Jiaxing,&Zhang Yingmei.(2017).Sirt3 deficiency exacerbates diabetic cardiac dysfunction: Role of Foxo3A-Parkin-mediated mitophagy .BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,1863(8):1973-1983.
MLA：

Yu Wenjun, et al. "Sirt3 deficiency exacerbates diabetic cardiac dysfunction: Role of Foxo3A-Parkin-mediated mitophagy" .BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 1863,8(2017):1973-1983.

浏览次数：1  下载次数：0

分享到：

浏览次数：1

下载次数：0

打印次数：0