Abstract
Resveratrol (RSV) is used as a protective therapy against diabetic retinopathy. However, the mechanism(s) underlying this protective effect has not been fully elucidated. Bovine retinal capillary endothelial cells (BRECs), an in vitro model, were used to investigate the mechanism of RSV. Our results showed that high glucose induced significant cellular apoptosis in BRECs, which was accompanied by increased intracellular levels of reactive oxygen species (ROS) and cleaved caspase-3. The glucose-induced apoptosis and ROS elevation were both inhibited by RSV. High glucose was found to decrease the levels of phosphorylated AMP-activated protein kinase (p-AMPK), which was accompanied by increased levels of Sirt1 and PGC-1α. These changes were reversed by RSV. We also demonstrated that AMPK regulates the modulations of Sirt1 and PGC-1α using specific inhibitors of AMPK and Sirt1 and small interfering RNAs of PGC-1α. In summary, the current study demonstrates that RSV is effective against high glucose-induced cellular apoptosis and its action is exerted via the inhibition of ROS/AMPK/Sirt1/PGC-1α pathway.
Highlights
Diabetic retinopathy (DR) is one of the major causes of severe vision loss and blindness in the working-age population [1]
A hypothesis has been proposed that high blood glucose induces oxidative stress through the generation of excessive reactive oxygen species (ROS), which play a dominant role in the development of chronic complications caused by diabetes, including retinopathy [7, 8]
Bovine retinal capillary endothelial cells (BRECs) were isolated from tissues obtained from a local slaughterhouse and cultured following protocols described previously [26]
Summary
Diabetic retinopathy (DR) is one of the major causes of severe vision loss and blindness in the working-age population [1]. Apoptosis of endothelial cells of the retinal vasculature plays a vital role in the pathogenesis of DR [4, 5]. High glucose (HG), an independent risk factor for diabetes, has been shown to induce apoptosis in retinal capillary endothelial cells [5, 6]. A hypothesis has been proposed that high blood glucose induces oxidative stress through the generation of excessive reactive oxygen species (ROS), which play a dominant role in the development of chronic complications caused by diabetes, including retinopathy [7, 8]. Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) is an important mediator of the metabolic effects of ROS, where PGC-1α activation results in the increase of mitochondrial energy metabolism and the cellular capacity to detoxify ROS, thereby reprogramming cell metabolism to maintain survival [10,11,12,13]
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