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

Cristian Gonzalez-Ruiz, Paola Cordero-Anguiano, Axayacatl Morales-Guadarrama, Rodrigo Mondragón-Lozano, Stephanie Sánchez-Torres, Hermelinda Salgado-Ceballos, Francisco Villarreal, Eduardo Meaney, Guillermo Ceballos, Nayelli Nájera

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)8975-8985
Number of pages11
JournalMolecular Biology Reports
Volume47
Issue number11
DOIs
StatePublished - Nov 2020

Keywords

  • (−)-Epicatechin
  • FOXO1a
  • MAFbx
  • MuRF1
  • Muscle atrophy
  • Spinal cord injury

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