Exercise training prevents skeletal muscle damage in an experimental sepsis model

OBJECTIVE: Oxidative stress plays an important role in skeletal muscle damage in sepsis. Aerobic exercise can decrease oxidative stress and enhance antioxidant defenses. Therefore, it was hypothesized that aerobic exercise training before a sepsis stimulus could attenuate skeletal muscle damage by modulating oxidative stress. Thus, the aim of this study was to evaluate the effects of aerobic physical preconditioning on the different mechanisms that are involved in sepsis-induced myopathy. METHODS: Male Wistar rats were randomly assigned to either the untrained or trained group. The exercise training protocol consisted of an eight-week treadmill program. After the training protocol, the animals from both groups were randomly assigned to either a sham group or a cecal ligation and perforation surgery group. Thus, the groups were as follows: sham, cecal ligation and perforation, sham trained, and cecal ligation and perforation trained. Five days after surgery, the animals were euthanized and their soleus and plantaris muscles were harvested. Fiber cross-sectional area, creatine kinase, thiobarbituric acid reactive species, carbonyl, catalase and superoxide dismutase activities were measured. RESULTS: The fiber cross-sectional area was smaller, and the creatine kinase, thiobarbituric acid reactive species and carbonyl levels were higher in both muscles in the cecal ligation and perforation group than in the sham and cecal ligation and perforation trained groups. The muscle superoxide dismutase activity was higher in the cecal ligation and perforation trained group than in the sham and cecal ligation and perforation groups. The muscle catalase activity was lower in the cecal ligation and perforation group than in the sham group. CONCLUSION: In summary, aerobic physical preconditioning prevents atrophy, lipid peroxidation and protein oxidation and improves superoxide dismutase activity in the skeletal muscles of septic rats

Aerobic exercise training rescues cardiac protein quality control and blunts endoplasmic reticulum stress in heart failure rats

Cardiac endoplasmic reticulum (ER) stress through accumulation of misfolded proteins plays a pivotal role in cardiovascular diseases. In an attempt to reestablish ER homoeostasis, the unfolded protein response (UPR) is activated. However, if ER stress persists, sustained UPR activation leads to apoptosis. There is no available therapy for ER stress relief. Considering that aerobic exercise training (AET) attenuates oxidative stress, mitochondrial dysfunction and calcium imbalance, it may be a potential strategy to reestablish cardiac ER homoeostasis. We test the hypothesis that AET would attenuate impaired cardiac ER stress after myocardial infarction (MI). Wistar rats underwent to either MI or sham surgeries. Four weeks later, rats underwent to 8 weeks of moderate‐intensity AET. Myocardial infarction rats displayed cardiac dysfunction and lung oedema, suggesting heart failure. Cardiac dysfunction in MI rats was paralleled by increased protein levels of UPR markers (GRP78, DERLIN‐1 and CHOP), accumulation of misfolded and polyubiquitinated proteins, and reduced chymotrypsin‐like proteasome activity. These results suggest an impaired cardiac protein quality control. Aerobic exercise training improved exercise capacity and cardiac function of MI animals. Interestingly, AET blunted MI‐induced ER stress by reducing protein levels of UPR markers, and accumulation of both misfolded and polyubiquinated proteins, which was associated with restored proteasome activity. Taken together, our study provide evidence for AET attenuation of ER stress through the reestablishment of cardiac protein quality control, which contributes to better cardiac function in post‐MI heart failure rats. These results reinforce the importance of AET as primary non‐pharmacological therapy to cardiovascular disease

Mitophagy and mitochondrial fission in soleus muscle.

<p>Soleus Bnip3 (<b>A</b>), DRP1 (<b>B</b>) and Fis1 (<b>C</b>) protein levels, and representative immunoblots (<b>D</b>) in Sham and MI groups. Correlation between soleus <i>BNIP3</i> mRNA levels and distance run in a graded treadmill exercise test (<b>E</b>, Sham n = 8, MI n = 10). Data presented as mean ± SEM. The number of animals in each analysis is shown within the bars.</p

Autophagic marker in plantaris muscle.

<p>Plantaris LC3-I (<b>A</b>) and LC3-II (<b>B</b>) protein levels, LC3-II/LC3-I ratio (<b>C</b>) and representative imunnoblots (<b>D</b>) in Sham and MI groups. Correlation between plantaris LC3-II protein expression and distance run in a graded treadmill exercise test (<b>E</b>, Sham n = 9, MI n = 10). Data presented as mean ± SEM. AU, arbitrary unit. The number of animals in each analysis is shown within the bars.</p

qRT-PCR Primer Sequences.

<p>qRT-PCR Primer Sequences.</p

Skeletal muscle autophagy-related genes expression.

<p>Soleus (<b>A</b>) and plantaris (<b>B</b>) <i>BECN1</i>, <i>ATG7</i>, <i>MAP1LC3B</i>, <i>GABARAPL1</i>, <i>ATG12</i>, <i>BNIP3</i>, <i>LAMP2</i> and <i>CTSL1</i> mRNA levels of in Sham and MI groups. Data presented as mean ± SEM. *indicates p≤0.05 vs. Sham. In soleus muscle were analyzed 11 animals in Sham group and 10 animals in MI group. In plantaris muscle were analyzed 11 animals in each group.</p