TY - JOUR
T1 - Sarcopenia in a mice model of chronic liver disease
T2 - role of the ubiquitin–proteasome system and oxidative stress
AU - Campos, Fabián
AU - Abrigo, Johanna
AU - Aguirre, Francisco
AU - Garcés, Bruno
AU - Arrese, Marco
AU - Karpen, Saul
AU - Cabrera, Daniel
AU - Andía, Marcelo E.
AU - Simon, Felipe
AU - Cabello-Verrugio, Claudio
N1 - Funding Information:
Acknowledgements This study was supported by research grants from the National Fund for Science & Technology Development [FONDECYT 1161646 (C.C.V.), 1161288 (F.S.); 11171001 (D.C.); 1150327 (M.A.)], Millennium Institute on Immunology and Immunotherapy [P09-016-F (F.S.)]; Programa de Cooperación Científica ECOS-CONICYT [C16S02 (C.C.V.)]; Center for Aging and Regeneration [CARE PFB12/2007 (M.A.)]; Fondequip EQM [150033 (M.E.A.)]; UNAB-DI [741-15/N (C.C.V., F.S.)]. J.A. thanks Conicyt for providing a PhD Scholarship (21161353). F.C. thanks Universidad Andrés Bello-Dirección de Investigación for providing a PhD Scholarship.
PY - 2018/6/20
Y1 - 2018/6/20
N2 - Sarcopenia is the loss of muscle mass and strength produced by aging or secondary to chronic diseases such as chronic liver disease (CLD). Although not all types of sarcopenia involve the same features, the most common are decreased fiber diameter and myosin heavy chain (MHC) levels, increased activity of ubiquitin–proteasome system (UPS) and reactive oxygen species (ROS). In this study, we aim to characterize the development of sarcopenia secondary to CLD induced by the hepatotoxin 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). For this purpose, four-months-old male C57BL6 mice were fed with normal diet or DDC supplemented diet for 6 weeks. Functional tests to evaluate muscle strength, mobility, and motor skills were performed in alive mice. The muscle strength in isolated gastrocnemius was also assayed via electrophysiological measurements. Morphometric measures of fibers’ diameter, total and ubiquitinated protein levels of myosin heavy chain (MHC), E3 ubiquitin ligases, ROS, and oxidation-dependent modified proteins in gastrocnemius tissue were also determined. Our results demonstrated that mice fed the DDC diet developed muscle wasting as evidenced by a loss of muscle mass and decreased muscle strength. The muscles of mice fed with DDC diet have a decreased diameter of fibers and MHC levels, also as increased MuRF-1 and atrogin-1 protein levels, ROS levels, and oxidation-modified protein levels. Additionally, control and DDC mice have the same food and water intake as well as mobility. Our results demonstrate mice with CLD develop sarcopenia involving decreased levels of myofibrillar proteins, increased UPS, and oxidative stress, but not for impaired caloric intake or immobility.
AB - Sarcopenia is the loss of muscle mass and strength produced by aging or secondary to chronic diseases such as chronic liver disease (CLD). Although not all types of sarcopenia involve the same features, the most common are decreased fiber diameter and myosin heavy chain (MHC) levels, increased activity of ubiquitin–proteasome system (UPS) and reactive oxygen species (ROS). In this study, we aim to characterize the development of sarcopenia secondary to CLD induced by the hepatotoxin 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). For this purpose, four-months-old male C57BL6 mice were fed with normal diet or DDC supplemented diet for 6 weeks. Functional tests to evaluate muscle strength, mobility, and motor skills were performed in alive mice. The muscle strength in isolated gastrocnemius was also assayed via electrophysiological measurements. Morphometric measures of fibers’ diameter, total and ubiquitinated protein levels of myosin heavy chain (MHC), E3 ubiquitin ligases, ROS, and oxidation-dependent modified proteins in gastrocnemius tissue were also determined. Our results demonstrated that mice fed the DDC diet developed muscle wasting as evidenced by a loss of muscle mass and decreased muscle strength. The muscles of mice fed with DDC diet have a decreased diameter of fibers and MHC levels, also as increased MuRF-1 and atrogin-1 protein levels, ROS levels, and oxidation-modified protein levels. Additionally, control and DDC mice have the same food and water intake as well as mobility. Our results demonstrate mice with CLD develop sarcopenia involving decreased levels of myofibrillar proteins, increased UPS, and oxidative stress, but not for impaired caloric intake or immobility.
KW - Chronic liver diseases
KW - Hepatotoxin
KW - Oxidative stress
KW - Sarcopenia
KW - UPS
UR - http://www.scopus.com/inward/record.url?scp=85048833830&partnerID=8YFLogxK
U2 - 10.1007/s00424-018-2167-3
DO - 10.1007/s00424-018-2167-3
M3 - Article
AN - SCOPUS:85048833830
SN - 0031-6768
VL - 470
SP - 1
EP - 17
JO - Pflugers Archiv European Journal of Physiology
JF - Pflugers Archiv European Journal of Physiology
IS - 10
ER -