Mechanistic Links Between Oxidative Stress and Disuse Muscle Atrophy

Powers, Scott K.; Smuder, Ashley J.; Criswell, David S.

doi:10.1089/ars.2011.3973

Cited by 161 publications

(147 citation statements)

References 77 publications

(108 reference statements)

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…It is yet not clear how extreme inactivity is enhancing lung disease but it is tempting to relate these findings to an excess of oxidative stress. A similar phenomenon is observed in skeletal muscles (41,42) in which physical inactivity, through oxidative stress, can lead to activation of inflammatory (43,44) and proteolytic pathways (41,42). Otherwise, enhanced lung inflammation in extremely inactive mice might be related to the fact that hindlimb suspension caused a redistribution of body fluids towards the upper body parts.…”

Section: Discussionmentioning

confidence: 53%

Interaction between Physical Activity and Smoking on Lung, Muscle, and Bone in Mice

Cielen

Maes

Heulens

et al. 2016

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Physical inactivity is an important contributor to skeletal muscle weakness, osteoporosis and weight loss in chronic obstructive pulmonary disease. However, the effects of physical inactivity, in interaction with smoking, on lung, muscle and bone are poorly understood. To address this issue, male mice were randomly assigned into an active (daily running), moderately inactive (space restriction) or extremely inactive group (space restriction followed by hindlimb suspension to mimic bed rest) during 24 weeks and simultaneously exposed to either cigarette smoke or room air. The effects of different physical activity levels and smoking status and their respective interaction were examined on lung function, body composition, in vitro limb muscle function and bone parameters. Smoking caused emphysema, reduced food intake with subsequent loss of body weight, fat, lean and muscle mass but increased trabecular bone volume. Smoking induced muscle fiber atrophy which did not result in force impairment. Moderate inactivity only affected lung volumes and compliance, whereas extreme inactivity increased lung inflammation, lowered body and fat mass, induced fiber atrophy with soleus muscle dysfunction and reduced exercise capacity and all bone parameters. When combined with smoking, extreme inactivity also aggravated lung inflammation and emphysema, and accelerated body and muscle weight loss. This study shows that extreme inactivity, especially when imposed by absolute rest, accelerates lung damage and inflammation. When combined with smoking, extreme inactivity is deleterious for muscle bulk, bone and lungs. These data highlight that the consequences of physical inactivity during the course of COPD should not be neglected.

show abstract

Section: Discussionmentioning

confidence: 53%

Interaction between Physical Activity and Smoking on Lung, Muscle, and Bone in Mice

Cielen

Maes

Heulens

et al. 2016

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…First, oxidative stress promotes increased gene expression of key proteins involved in both autophagy and the ubiquitin-proteasome system (reviewed in Ref. 88). Presumably this ROS-mediated gene expression occurs due to redoxsensitive transcriptional activating factors (e.g., NF B, FoxO3a, etc.)…”

Section: R468mentioning

confidence: 99%

“…Also, MV-induced ROS production in skeletal muscle has been shown to activate calpain (82,117). The specific mechanism(s) responsible for this ROS-mediated activation of calpain has not been studied but is potentially linked to ROS-mediated increases in cytosolic free calcium (37,88). Finally, MV-induced oxidative stress has also been shown to activate caspase-3 in the diaphragm (82,117).…”

Section: R468mentioning

confidence: 99%

Ventilator-induced diaphragm dysfunction: cause and effect

Powers

Wiggs

Sollanek

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

143

156

View full text Add to dashboard Cite

Powers SK, Wiggs MP, Sollanek KJ, Smuder AJ. Ventilator-induced diaphragm dysfunction: cause and effect. Am J Physiol Regul Integr Comp Physiol 305: R464 -R477, 2013. First published July 10, 2013 doi:10.1152/ajpregu.00231.2013 is used clinically to maintain gas exchange in patients that require assistance in maintaining adequate alveolar ventilation. Common indications for MV include respiratory failure, heart failure, drug overdose, and surgery. Although MV can be a life-saving intervention for patients suffering from respiratory failure, prolonged MV can promote diaphragmatic atrophy and contractile dysfunction, which is referred to as ventilator-induced diaphragm dysfunction (VIDD). This is significant because VIDD is thought to contribute to problems in weaning patients from the ventilator. Extended time on the ventilator increases health care costs and greatly increases patient morbidity and mortality. Research reveals that only 18 -24 h of MV is sufficient to develop VIDD in both laboratory animals and humans. Studies using animal models reveal that MV-induced diaphragmatic atrophy occurs due to increased diaphragmatic protein breakdown and decreased protein synthesis. Recent investigations have identified calpain, caspase-3, autophagy, and the ubiquitin-proteasome system as key proteases that participate in MV-induced diaphragmatic proteolysis. The challenge for the future is to define the MV-induced signaling pathways that promote the loss of diaphragm protein and depress diaphragm contractility. Indeed, forthcoming studies that delineate the signaling mechanisms responsible for VIDD will provide the knowledge necessary for the development of a pharmacological approach that can prevent VIDD and reduce the incidence of weaning problems. respiratory muscle; atrophy; mechanical ventilation; weaning; muscle wasting MECHANICAL VENTILATION (MV) is used clinically to achieve sufficient pulmonary gas exchange in patients unable to sustain adequate alveolar ventilation on their own. Common indications for MV include respiratory failure due to chronic obstructive pulmonary disease, status asthmaticus, and/or heart failure. In addition, MV is often an essential intervention in patients suffering from acute drug overdose, neuromuscular diseases, sepsis, and during surgery along with postsurgical recovery.The number of patients receiving prolonged MV in the United States exceeds more than 300,000 each year in the intensive care unit (ICU) (20). Although MV can be a lifesaving measure, prolonged MV results in the rapid development of diaphragmatic weakness due to both atrophy and contractile dysfunction. This detrimental impact of prolonged MV on the diaphragm has been termed ventilator-induced diaphragmatic dysfunction (VIDD) and VIDD is predicted to be a major contributor to problems in weaning patients from the ventilator (26, 114). Although previous reports describing the impact of prolonged MV on the diaphragm have appeared in the literature, advances in our understanding of the mechanisms responsible for VIDD h...

show abstract

“…Because oxidative stress can promote disuse atrophy (21,22), we used a Trolox equivalent antioxidant capacity assay (23) to determine whether either inhibitor possessed antioxidant properties. Our results reveal that neither protease inhibitor (e.g., SJA-6017 or Ac-DEVD-CHO) quenched the oxidants used in the assay (data not shown).…”

Section: Pharmacological Inhibitorsmentioning

confidence: 99%