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

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 7days, (2) Spinal cord injury + (-)-epicatechin 7days, (3) Spinal cord injury 30days, (4) Spinal cord injury + (-)-epicatechin 30days 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 30days 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 30days. At 7 and 30days 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.