Resveratrol-enhanced autophagic flux ameliorates myocardial oxidative stress injury in diabetic mice

نویسندگان

  • Bo Wang
  • Qing Yang
  • Yuan-yuan Sun
  • Yi-fan Xing
  • Ying-bin Wang
  • Xiao-ting Lu
  • Wen-wu Bai
  • Xiao-qiong Liu
  • Yu-xia Zhao
چکیده

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 (SIRT1) 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 SIRT1 activity and Rab7 expression. Inhibiting autophagic flux with bafilomycin A1 increased diabetic mouse mortality and attenuated resveratrol-induced down-regulation of p62, but not SIRT1 activity or Rab7 expression in diabetic mouse hearts. In cultured H9C2 cells, redundant or overactive H₂O₂ increased p62 and cleaved caspase 3 expression as well as acetylated forkhead box protein O1 (FOXO1) and inhibited SIRT1 expression. Sirtinol, SIRT1 and Rab7 siRNA impaired the resveratrol amelioration of dysfunctional autophagic flux and reduced apoptosis under oxidative conditions. Furthermore, resveratrol enhanced FOXO1 DNA binding at the Rab7 promoter region through a SIRT1-dependent pathway. These results highlight the role of the SIRT1/FOXO1/Rab7 axis in the effect of resveratrol on autophagic flux in vivo and in vitro, which suggests a therapeutic strategy for diabetic cardiomyopathy.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Oxidative stress stimulates autophagic flux during ischemia/reperfusion.

Autophagy is a bulk degradation process in which cytosolic proteins and organelles are degraded through lysosomes. To evaluate autophagic flux in cardiac myocytes, we generated adenovirus and cardiac-specific transgenic mice harboring tandem fluorescent mRFP-GFP-LC3. Starvation significantly increased the number of mRFP-GFP-LC3 dots representing both autophagosomes and autolysosomes per cell, s...

متن کامل

Resveratrol ameliorates myocardial fibrosis by inhibiting ROS/ERK/TGF-β/periostin pathway in STZ-induced diabetic mice

BACKGROUND Myocardial fibrosis is an essential hallmark of diabetic cardiomyopathy (DCM) contributing to cardiac dysfunctions. Resveratrol, an antioxidant, exerts its anti-fibrotic effect via inhibition of oxidative stress, while the underlying molecular mechanism remains largely elusive. Periostin, a fibrogenesis matricellular protein, has been shown to be associated with oxidative stress. In ...

متن کامل

Resveratrol ameliorates autophagic flux to promote functional recovery in rats after spinal cord injury

Resveratrol is known to improve functional recovery after spinal cord injury, but the exact mechanism involved is yet unclear. The aim of this study was to clarify whether resveratrol can exert neuroprotective effects via activating neuronal autophagic flux, in view of the underlying role of the autophagic flux mediated by resveratrol on neuronal apoptosis after spinal cord injury, and identify...

متن کامل

Reduced HMGB 1-Mediated Pathway and Oxidative Stress in Resveratrol-Treated Diabetic Mice: A Possible Mechanism of Cardioprotection of Resveratrol in Diabetes Mellitus

Myocardial fibrosis and inflammation are intricately linked in diabetic cardiomyopathy (DCM), and resveratrol has been shown to attenuate oxidative stress, inflammation, and fibrosis in several cell types or animal models. High mobility group box 1 (HMGB 1), a proinflammatory cytokine, has been reported to regulate fibrosis and inflammation in various organs. Then the present study aimed to rev...

متن کامل

Resveratrol Improves Oxidative Stress and Protects Against Diabetic Nephropathy Through Normalization of Mn-SOD Dysfunction in AMPK/SIRT1-Independent Pathway

OBJECTIVE Despite the beneficial effects of resveratrol (RSV) on cardiovascular disease and life span, its effects on type 2 diabetic nephropathy remain unknown. This study examined the renoprotective effects of RSV in db/db mice, a model of type 2 diabetes. RESEARCH DESIGN AND METHODS db/db mice were treated with RSV (0.3% mixed in chow) for 8 weeks. We measured urinary albumin excretion (UA...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 18  شماره 

صفحات  -

تاریخ انتشار 2014