<b>Time course of ubiquitin-proteasome and macroautophagy-lysosome pathways in skeletal muscle in rats with heart failur</b><b>e </b>

Abstract

Patients with heart failure have limited exercise capacity due to not only the myocardial dysfunction but also skeletal muscle atrophy. However, the mechanisms and time course of protein degradation in skeletal muscle during heart failure remain unclear, and there is no established standard treatment. The purpose of the present study was to investigate the time course of major protein degradation pathways in skeletal muscle during heart failure. Four-week-old male Wistar rats were randomly assigned to heart failure induced by monocrotaline or control groups. At 14 and 21 days after monocrotaline injection, the lungs, heart, and gastrocnemius and soleus muscles were removed and analyzed. There was no significant difference in body weight between the groups at 14 days after monocrotaline injection. Although there were no morphological changes in the skeletal muscle of the monocrotaline group at this time point, ubiquitin-proteasome and macroautophagylysosome pathways were activated in the monocrotaline group. Additionally, the pathways were less strongly activated in the soleus muscle than in the gastrocnemius muscle. These results suggest that physical exercise that shifts to slow muscle characteristics should begin when there is no indication of skeletal muscle atrophy to prevent exercise intolerance with heart failure.Patients with heart failure have limited exercise capacity due to not only myocardial dysfunction, but also skeletal muscle atrophy (6) and reduced strength (8). Skeletal muscle atrophy and consequent strength reduction result from various conditions such as muscular inactivity, sarcopenia, and cachexia, which decrease protein synthesis and increase protein degradation (17). Similarly, decreased protein synthesis (27) and increased protein degradation (4) after heart failure contribute to skeletal muscle atrophy, and protein degradation is especially common in chronic cases. Some protein degradation pathways involved in skeletal muscle atrophy, namely ubiquitin-proteasome and macroautophagy-lysosome pathways are delineated as major protein degradation system. Ubiquitinproteasome pathway activity is increased in atrophied

Neutralization of GDF15 Prevents Anorexia and Weight Loss in the Monocrotaline-Induced Cardiac Cachexia Rat Model

“…Increased protein breakdown by activation of catabolism genes in muscle has been implicated in muscle wasting in cachexia [ 33 , 34 ]. MCT was reported to induce the expression of Trim63 (MurF1) and Fbox32 (Atrogin-1), two E3 ligases involved in protein ubiquitination and degradation in muscle [ 35 , 36 ]. We measured the expression of Trim63 (MurF1) and Fbox32, as well as their upstream regulator Foxo1 in tibialis anterior muscle.…”

Muscle wasting and cachexia in heart failure: mechanisms and therapies

“…In summary, autophagy is involved in muscle maintenance, but autophagy induced under catabolic conditions might be detrimental. Evidence suggests that both the UPS and autophagy are induced in skeletal muscle early in the course of HF 114,115 .…”

Hyperbaric Normoxia Improved Glucose Metabolism and Decreased Inflammation in Obese Diabetic Rat

“…Skeletal muscle atrophy in type 2 diabetes is associated with physical inactivity, reduced food intake, and peripheral neuropathy. Therefore, the defects in the skeletal muscle mass of OLETF rats may have been caused by the downregulation of protein synthesis which may occur as a result of physical inactivity [34, 35], immobilization [36, 37], denervation [38], and cachexia [39]. Hyperbaric treatment does not seem to enhance structural protein synthesis in the skeletal muscle.…”