Polydatin enhances glomerular podocyte autophagy homeostasis by improving Nrf2-dependent antioxidant capacity in fructose-fed rats

Mol Cell Endocrinol. 2021 Jan 15:520:111079. doi: 10.1016/j.mce.2020.111079. Epub 2020 Nov 12.

Abstract

High fructose is considered a causative factor for oxidative stress and autophagy imbalance that cause kidney pathogenesis. Antioxidant polydatin isolated from Polygonum cuspidatum has been reported to protect against kidney injury. In this study, polydatin was found to ameliorate fructose-induced podocyte injury. It activated mammalian target of rapamycin complex 1 (mTORC1) and suppressed autophagy in glomeruli of fructose-fed rats and in fructose-exposed conditionally immortalized human podocytes (HPCs). Polydatin also enhanced nuclear factor-E2-related factor 2 (Nrf2)-dependent antioxidant capacity to suppress fructose-induced autophagy activation in vivo and in vitro, with the attenuation of fructose-induced up-regulation of cellular light chain 3 (LC3) II/I protein levels. This effect was abolished by Raptor siRNA in fructose-exposed HPCs. These results demonstrated that polydatin ameliorated fructose-induced autophagy imbalance in an mTORC1-dependent manner via improving Nrf2-dependent antioxidant capacity during podocyte injury. In conclusion, polydatin with anti-oxidation activity suppressed autophagy to protect against fructose-induced podocyte injury.

Keywords: Autophagy; Fructose; Oxidative stress; Podocyte injury; Polydatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Adenylate Kinase / metabolism
  • Animals
  • Antioxidants / metabolism*
  • Autophagy* / drug effects
  • Feeding Behavior*
  • Fructose
  • Glucosides / pharmacology*
  • Homeostasis* / drug effects
  • Humans
  • Male
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Podocytes / drug effects
  • Podocytes / metabolism*
  • Podocytes / pathology
  • Proteinuria / complications
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antioxidants
  • Glucosides
  • NF-E2-Related Factor 2
  • Stilbenes
  • Fructose
  • Adenosine Triphosphate
  • Mechanistic Target of Rapamycin Complex 1
  • p38 Mitogen-Activated Protein Kinases
  • Adenylate Kinase
  • polydatin