Open AccessResveratrol‐enhanced autophagic flux ameliorates myocardial oxidative stress injury in diabetic mice
Author(s) -
Wang Bo,
Yang Qing,
Sun Yuanyuan,
Xing Yifan,
Wang Yingbin,
Lu Xiaoting,
Bai Wenwu,
Liu Xiaoqiong,
Zhao Yuxia
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12312
Subject(s) - resveratrol , autophagy , diabetic cardiomyopathy , sirtuin 1 , oxidative stress , sirtuin , apoptosis , pharmacology , streptozotocin , microbiology and biotechnology , diabetes mellitus , chemistry , downregulation and upregulation , endocrinology , medicine , biology , cardiomyopathy , heart failure , acetylation , biochemistry , gene
Autophagic dysfunction is observed in diabetes mellitus. Resveratrol has a beneficial effect on diabetic cardiomyopathy. Whether the resveratrol‐induced improvement in cardiac function in diabetes is via regulating autophagy remains unclear. We investigated the mechanisms underlying resveratrol‐mediated protection against heart failure in diabetic mice, with a focus on the role of sirtuin 1 ( SIRT 1) in regulating autophagic flux. Diabetic cardiomyopathy in mice was induced by streptozotocin ( STZ ). Long‐term resveratrol treatment improved cardiac function, ameliorated oxidative injury and reduced apoptosis in the diabetic mouse heart. Western blot analysis revealed that resveratrol decreased p62 protein expression and promoted SIRT 1 activity and Rab7 expression. Inhibiting autophagic flux with bafilomycin A1 increased diabetic mouse mortality and attenuated resveratrol‐induced down‐regulation of p62, but not SIRT 1 activity or Rab7 expression in diabetic mouse hearts. In cultured H9C2 cells, redundant or overactive H 2 O 2 increased p62 and cleaved caspase 3 expression as well as acetylated forkhead box protein O1 ( FOXO 1) and inhibited SIRT 1 expression. Sirtinol, SIRT 1 and Rab7 si RNA impaired the resveratrol amelioration of dysfunctional autophagic flux and reduced apoptosis under oxidative conditions. Furthermore, resveratrol enhanced FOXO 1 DNA binding at the Rab7 promoter region through a SIRT 1‐dependent pathway. These results highlight the role of the SIRT 1/ FOXO 1/Rab7 axis in the effect of resveratrol on autophagic flux in vivo and in vitro , which suggests a therapeutic strategy for diabetic cardiomyopathy.