TY - JOUR
T1 - (−)-Epicatechin reduces muscle waste after complete spinal cord transection in a murine model
T2 - role of ubiquitin–proteasome system
AU - Gonzalez-Ruiz, Cristian
AU - Cordero-Anguiano, Paola
AU - Morales-Guadarrama, Axayacatl
AU - Mondragón-Lozano, Rodrigo
AU - Sánchez-Torres, Stephanie
AU - Salgado-Ceballos, Hermelinda
AU - Villarreal, Francisco
AU - Meaney, Eduardo
AU - Ceballos, Guillermo
AU - Nájera, Nayelli
N1 - Publisher Copyright:
© 2020, Springer Nature B.V.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - (−)-Epicatechin
KW - FOXO1a
KW - MAFbx
KW - MuRF1
KW - Muscle atrophy
KW - Spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=85095127290&partnerID=8YFLogxK
U2 - 10.1007/s11033-020-05954-x
DO - 10.1007/s11033-020-05954-x
M3 - Artículo
C2 - 33151476
AN - SCOPUS:85095127290
SN - 0301-4851
VL - 47
SP - 8975
EP - 8985
JO - Molecular Biology Reports
JF - Molecular Biology Reports
IS - 11
ER -