Resveratrol ameliorates podocyte damage in diabetic mice via SIRT1/PGC-1α mediated attenuation of mitochondrial oxidative stress.

Excessive generation of mitochondrial reactive oxygen species (ROS) is considered to be initiating event in the development of diabetic nephropathy (DN). Mitochondrial biosynthesis mediated by coactivator PGC-1α and its downstream transcription factors NRF1 and TFAM may be a key target in maintaining mitochondrial function. Resveratrol (RESV), a natural polyphenolic antioxidant, is a potent SIRT1 agonist. In this study we established diabetes mouse and podocyte exposed to high glucose as in vivo and in vitro models to investigate the efficacy and mechanism of RESV on renoprotection. We found that RESV alleviated proteinuria of diabetic mice, decreased malondialdehyde content while increased Mn-SOD activity in renal cortex, inhibited the apoptosis of glomerular podocytes and renal tubular epithelial cells, ameliorated pathological manifestations, and restored the expression of SIRT1 and PGC-1α in renal tissues of DN mice. In podocytes exposed to high glucose, RESV inhibited excessive ROS production and apoptosis. In addition, RESV decreased mitochondrial ROS production, improved respiratory chain complex I and III activity, elevated mitochondrial membrane potential, and inhibited the release of Cyto C and Diablo in the mitochondria into the cytoplasm. Taken together, our findings suggest that RESV ameliorates podocyte damage in diabetic mice via SIRT1/PGC-1α mediated attenuation of mitochondrial oxidative stress.