Resveratrol attenuates denervation-induced muscle atrophy due to the blockade of atrogin-1 and p62 accumulation

Int J Med Sci. 2018 Apr 3;15(6):628-637. doi: 10.7150/ijms.22723. eCollection 2018.

Abstract

Decrease in activity stress induces skeletal muscle atrophy. A previous study showed that treatment with resveratrol inhibits muscular atrophy in mdx mice, a model of DMD. However, almost all studies using resveratrol supplementation have only looked at adaptive changes in the muscle weight. The present study was designed to elucidate whether the resveratrol-inducing attenuation of skeletal muscle actually reflects the adaptation of muscle fibers themselves, based on the modulation of atrogin-1- or p62-dependent signaling. Mice were fed either a normal diet or 0.5% resveratrol diet. One week later, the right sciatic nerve was cut. The wet weight, mean fiber area, and amount of atrogin-1 and p62 proteins were examined in the gastrocnemius muscle at 14 days after denervation. The 0.5% resveratrol diet significantly prevented denervation-induced decreases in both the muscle weight and fiber atrophy. In addition, dietary resveratrol suppressed the denervation-induced atrogin-1 and p62 immunoreactivity. In contrast, 0.5% resveratrol supplementation did not significantly modulate the total protein amount of atrogin-1 or p62 in the denervated muscle of mice. Resveratrol supplementation significantly prevents muscle atrophy after denervation in mice, possibly due to the decrease in atrogin-1 and p62-dependent signaling.

Keywords: atrogin-1; denervation; muscle atrophy; p62; resveratrol; supplementation.

MeSH terms

  • Animals
  • Dietary Supplements*
  • Humans
  • Mice, Inbred mdx
  • Muscle Denervation / methods
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / pathology
  • Muscle Proteins / genetics
  • Muscular Atrophy / drug therapy*
  • Muscular Atrophy / genetics
  • Muscular Atrophy / physiopathology
  • Resveratrol
  • SKP Cullin F-Box Protein Ligases / genetics
  • Signal Transduction / drug effects
  • Stilbenes / administration & dosage*
  • Transcription Factor TFIIH
  • Transcription Factors / genetics

Substances

  • Gtf2h1 protein, mouse
  • Muscle Proteins
  • Stilbenes
  • Transcription Factors
  • Transcription Factor TFIIH
  • Fbxo32 protein, mouse
  • SKP Cullin F-Box Protein Ligases
  • Resveratrol