(-)-Epicatechin reduces muscle waste after complete spinal cord transection in a murine model: role of ubiquitin-proteasome system

Mol Biol Rep. 2020 Nov;47(11):8975-8985. doi: 10.1007/s11033-020-05954-x. Epub 2020 Nov 5.

Abstract

The skeletal muscle mass reduces 30-60% after spinal cord injury, this is mostly due to protein degradation through ubiquitin-proteasome system. In this work, we propose that the flavanol (-)-epicatechin, due its widespread biological effects on muscle health, can prevent muscle mass decrease after spinal cord injury. Thirty-six female Long Evans rats were randomized into 5 groups: (1) Spinal cord injury 7 days, (2) Spinal cord injury + (-)-epicatechin 7 days, (3) Spinal cord injury 30 days, (4) Spinal cord injury + (-)-epicatechin 30 days and (5) Sham (Only laminectomy). Hind limb perimeter, muscle cross section area, fiber cross section area and ubiquitin-proteasome system protein expression together with total protein ubiquitination were assessed. At 30 days Spinal cord injury group lost 49.52 ± 2.023% of muscle cross section area (-)-epicatechin treated group lost only 24.28 ± 15.45% being a significant difference. Ubiquitin-proteasome markers showed significant changes. FOXO1a increased in spinal cord injury group vs Sham (-)-epicatechin reduced this increase. In spinal cord injury group MAFbx increased significantly vs Sham but decrease in (-)-epicatechin treatment group at 30 days. At 7 and 30 days MuRF1 increased in the spinal cord injury and decreased in the (-)-epicatechin group. The global protein ubiquitination increases after spinal cord injury, epicatechin treatment induce a significant decrease in protein ubiquitination. These results suggest that (-)-epicatechin reduces the muscle waste after spinal cord injury through down regulation of the ubiquitin-proteasome system.

Keywords: (−)-Epicatechin; FOXO1a; MAFbx; MuRF1; Muscle atrophy; Spinal cord injury.

MeSH terms

  • Animals
  • Catechin / pharmacology*
  • Disease Models, Animal*
  • Female
  • Magnetic Resonance Imaging / methods
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / diagnostic imaging
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / prevention & control
  • Myofibrils / metabolism
  • Proteasome Endopeptidase Complex / metabolism*
  • Rats, Long-Evans
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology

Substances

  • Catechin
  • Proteasome Endopeptidase Complex